Natural Product-Based Glycolysis Inhibitors as a Therapeutic Strategy for Epidermal Growth Factor Receptor–Tyrosine Kinase Inhibitor-Resistant Non-Small Cell Lung Cancer
<p>Targeted therapies for lung cancer. Illustration of the current targeted therapies used for non-small cell lung cancer (NSCLC), with specific drugs targeting (<b>A</b>) <span class="html-italic">EGFR</span> mutations; (<b>B</b>) <span class="html-italic">ALK</span>, <span class="html-italic">HER2</span>, <span class="html-italic">MET</span>, <span class="html-italic">NTRK</span>, <span class="html-italic">RET</span>, and <span class="html-italic">ROS1</span> mutations; (<b>C</b>) <span class="html-italic">KRAS</span> and <span class="html-italic">BRAF</span> mutations; and (<b>D</b>) immunotherapy drugs for PD-L1 expression. This figure provides an outline of the targeted therapy choices recommended by the 2022 National Comprehensive Cancer Network guidelines for metastatic NSCLC, emphasizing the importance of personalized genetic testing in determining the optimal treatment strategy. <span class="html-italic">EGFR</span>, epidermal growth factor receptor; <span class="html-italic">ALK</span>, anaplastic lymphoma kinase; <span class="html-italic">HER2</span>, human epidermal growth factor receptor 2; <span class="html-italic">MET</span>, proto-oncogene, receptor tyrosine kinase; <span class="html-italic">NTRK</span>, neurotrophic tyrosine receptor kinase; <span class="html-italic">RET</span>, RET proto-oncogene; <span class="html-italic">ROS1</span>, ROS proto-oncogene 1, receptor tyrosine kinase; <span class="html-italic">KRAS</span>, Kirsten rat sarcoma virus; <span class="html-italic">BRAF</span>, v-raf murine sarcoma viral oncogene homolog B1; PD-L1, programmed cell death ligand 1.</p> "> Figure 2
<p>Timeline of non-small cell lung cancer targeted therapy. Illustration of the timeline of genetic alterations in non-small cell lung cancer (NSCLC) subtypes, including <span class="html-italic">EGFR</span>, <span class="html-italic">ALK</span>, <span class="html-italic">ROS1</span>, <span class="html-italic">KRAS</span>, <span class="html-italic">MET</span>, <span class="html-italic">PD-L1</span>, and other mutations. This figure also indicates major concerns regarding the development of targeted therapy for NSCLC. <span class="html-italic">EGFR</span>, epidermal growth factor receptor; <span class="html-italic">ALK</span>, anaplastic lymphoma kinase; <span class="html-italic">KRAS</span>, Kirsten rat sarcoma virus; MET, proto-oncogene, receptor tyrosine kinase; ROS1, ROS proto-oncogene 1, receptor tyrosine kinase; PD-L1, programmed cell death ligand 1.</p> "> Figure 3
<p>Schematic diagrams of EGFR, HER2, HER3, and HER4. The ErbB protein family includes the EGFR (HER1 and ErbB1), HER2 (Neu and ErbB2), HER3 (ErbB3), and HER4 (ErbB4) proteins. Structurally, EGFR comprises an extracellular domain containing a ligand-binding region, a transmembrane domain, a tyrosine kinase (TK) domain, and a C-terminal phosphorylation domain. Additionally, the binding of growth factors to these receptors is displayed: seven to EGFR, none to HER2, two to HER3, and seven to HER4. Compared with other ErbB protein family members (EGFR, HER2, and HER4), HER3 has little to no TK activity [<a href="#B56-ijms-25-00807" class="html-bibr">56</a>,<a href="#B57-ijms-25-00807" class="html-bibr">57</a>,<a href="#B58-ijms-25-00807" class="html-bibr">58</a>,<a href="#B59-ijms-25-00807" class="html-bibr">59</a>]. <span class="html-italic">EGFR</span>, epidermal growth factor receptor; <span class="html-italic">HER</span>, human epidermal growth factor receptor. ‘?‘ means that ‘None to HER2’ indicates there are presently no known HER2 ligands.</p> "> Figure 4
<p>Treatment strategy for <span class="html-italic">EGFR</span>-mutated non-small cell lung cancer (NSCLC). Illustration depicting the treatment strategy for NSCLC with <span class="html-italic">EGFR</span> mutations. The figure focuses on the glycolysis pathway, a key metabolic process in cancer cells. The glycolysis pathway is highlighted, with key enzymes, including HK2, PKM2, LDHA, and PDK1, marked in pink to emphasize their significance in the metabolic reprogramming of cancer cells. In the blue box, natural product-based glycolysis inhibitors are indicated, showcasing their potential role in targeting glycolytic pathways. Additionally, the figure underscores the regulatory influence of HIF-1α, depicted as a key factor (red), which can upregulate glycolytic enzymes, further emphasizing the intricate interplay within the glycolysis pathway. EGFR, epidermal growth factor receptor; HK2, hexokinase 2; PKM2, pyruvate kinase M2; LDHA, lactate dehydrogenase A; PDK, pyruvate dehydrogenase kinase; HIF-1α, hypoxia-inducible factor 1-alpha. The upward arrow symbol (↑) indicates upregulation.</p> ">
Abstract
:1. Introduction
2. Targeted Therapy in NSCLC
3. EGFR-TKIs in NSCLC Treatment
4. Enhanced Glycolysis in EGFR-TKI-Resistant NSCLC
5. Advantages of PDK Inhibition against EGFR-TKI Resistance and Inhibitors from Natural Products
6. Natural Product-Derived LDHA Inhibitors and Their Advantage against EGFR-TKI Resistance
7. Natural Products Suppressing Other Glycolytic Enzymes and Their Use for EGFR-TKI Resistance
8. Perspectives and Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
Abbreviation | Definition |
2-DG | 2-deoxy-d-glucose |
ALK | Anaplastic lymphoma kinase |
ATP | Adenosine triphosphate |
BRAF | V-raf murine sarcoma viral oncogene homolog B1 |
c-Myc | Cellular-myelocytomatosis oncogene |
DCA | Dichloroacetate |
DNA | Deoxyribonucleic acid |
EGCG | Epigallocatechin gallate |
EGF | Epidermal growth factor |
EGFR | Epidermal growth factor receptor |
FBP1 | Fructose-1,6-bisphosphatase |
FDA | Food and Drug Administration |
GLUT1 | Glucose transporter 1 |
HER2 | Human epidermal growth factor receptor 2 |
HIF-1α | Hypoxia-inducible factor-1 alpha |
HK2 | Hexokinase 2 |
KRAS | Kirsten rat sarcoma virus |
LDH | Lactate dehydrogenase |
LDHA | Lactate dehydrogenase A |
MET | Proto-oncogene, receptor tyrosine kinase |
NAD | Nicotinamide adenine dinucleotide |
NCCN | National Comprehensive Cancer Network |
ND | Not determined |
NSCLC | Non-small cell lung cancer |
NTRK | Neurotrophic tyrosine receptor kinase |
OXPHOS | Oxidative phosphorylation |
OR | Overall survival |
PDC | Pyruvate dehydrogenase complex |
PDK | Pyruvate dehydrogenase kinase |
PD-L1 | Programmed cell death ligand 1 |
PEP | Phosphoenolpyruvate |
PI3K | Phosphatidylinositol 3-kinase |
PKM2 | Pyruvate kinase M2 |
RET | RET proto-oncogene |
RNA | Ribonucleic acid |
ROS | Reactive oxygen species |
ROS1 | ROS proto-oncogene 1, receptor tyrosine kinase |
SCLC | Small cell lung cancer |
SFN | Sulforaphane |
TK | Tyrosine kinase |
TKI | Tyrosine kinase inhibitor |
References
- Wang, M.; Herbst, R.S.; Boshoff, C. Toward personalized treatment approaches for non-small-cell lung cancer. Nat. Med. 2021, 27, 1345–1356. [Google Scholar] [CrossRef] [PubMed]
- Molina, J.R.; Yang, P.; Cassivi, S.D.; Schild, S.E.; Adjei, A.A. Non-Small Cell Lung Cancer: Epidemiology, Risk Factors, Treatment, and Survivorship; Mayo Clinic Proceedings; Elsevier: Amsterdam, The Netherlands, 2008; pp. 584–594. [Google Scholar]
- Van Meerbeeck, J.P.; Fennell, D.A.; De Ruysscher, D.K. Small-cell lung cancer. Lancet 2011, 378, 1741–1755. [Google Scholar] [CrossRef] [PubMed]
- Halliday, P.R.; Blakely, C.M.; Bivona, T.G. Emerging targeted therapies for the treatment of non-small cell lung cancer. Curr. Oncol. Rep. 2019, 21, 21. [Google Scholar] [CrossRef] [PubMed]
- Li, K.; Yang, M.; Liang, N.; Li, S. Determining EGFR-TKI sensitivity of G719X and other uncommon EGFR mutations in non-small cell lung cancer: Perplexity and solution. Oncol. Rep. 2017, 37, 1347–1358. [Google Scholar] [CrossRef] [PubMed]
- Zhang, Y.-L.; Yuan, J.-Q.; Wang, K.-F.; Fu, X.-H.; Han, X.-R.; Threapleton, D.; Yang, Z.-Y.; Mao, C.; Tang, J.-L. The prevalence of EGFR mutation in patients with non-small cell lung cancer: A systematic review and meta-analysis. Oncotarget 2016, 7, 78985. [Google Scholar] [CrossRef] [PubMed]
- Inoue, A.; Kobayashi, K.; Usui, K.; Maemondo, M.; Okinaga, S.; Mikami, I.; Ando, M.; Yamazaki, K.; Saijo, Y.; Gemma, A. First-line gefitinib for patients with advanced non-small-cell lung cancer harboring epidermal growth factor receptor mutations without indication for chemotherapy. J. Clin. Oncol. 2009, 27, 1394–1400. [Google Scholar] [CrossRef] [PubMed]
- Ramalingam, S.S.; Vansteenkiste, J.; Planchard, D.; Cho, B.C.; Gray, J.E.; Ohe, Y.; Zhou, C.; Reungwetwattana, T.; Cheng, Y.; Chewaskulyong, B. Overall survival with osimertinib in untreated, EGFR-mutated advanced NSCLC. N. Engl. J. Med. 2020, 382, 41–50. [Google Scholar] [CrossRef] [PubMed]
- Leonetti, A.; Sharma, S.; Minari, R.; Perego, P.; Giovannetti, E.; Tiseo, M. Resistance mechanisms to osimertinib in EGFR-mutated non-small cell lung cancer. Br. J. Cancer 2019, 121, 725–737. [Google Scholar] [CrossRef]
- Varghese, E.; Samuel, S.M.; Líšková, A.; Samec, M.; Kubatka, P.; Büsselberg, D. Targeting Glucose Metabolism to Overcome Resistance to Anticancer Chemotherapy in Breast Cancer. Cancers 2020, 12, 2252. [Google Scholar] [CrossRef]
- Jeong, J.Y.; Jeoung, N.H.; Park, K.-G.; Lee, I.-K. Transcriptional regulation of pyruvate dehydrogenase kinase. Diabetes Metab. J. 2012, 36, 328–335. [Google Scholar] [CrossRef]
- Lu, C.-W.; Lin, S.-C.; Chen, K.-F.; Lai, Y.-Y.; Tsai, S.-J. Induction of pyruvate dehydrogenase kinase-3 by hypoxia-inducible factor-1 promotes metabolic switch and drug resistance. J. Biol. Chem. 2008, 283, 28106–28114. [Google Scholar] [CrossRef] [PubMed]
- Han, J.H.; Kim, M.; Choi, H.J.; Jin, J.S.; Lee, S.O.; Bae, S.J.; Ryu, D.; Ha, K.T. The Oral Administration of Sanguisorba officinalis Extract Improves Physical Performance through LDHA Modulation. Molecules 2021, 26, 1579. [Google Scholar] [CrossRef] [PubMed]
- Han, J.H.; Kim, M.; Kim, H.J.; Jang, S.B.; Bae, S.J.; Lee, I.K.; Ryu, D.; Ha, K.T. Targeting Lactate Dehydrogenase A with Catechin Resensitizes SNU620/5FU Gastric Cancer Cells to 5-Fluorouracil. Int. J. Mol. Sci. 2021, 22, 5406. [Google Scholar] [CrossRef] [PubMed]
- Newman, D.J.; Cragg, G.M. Natural products as sources of new drugs over the 30 years from 1981 to 2010. J. Nat. Prod. 2012, 75, 311–335. [Google Scholar] [CrossRef] [PubMed]
- Zhao, Y.; Chard Dunmall, L.S.; Cheng, Z.; Wang, Y.; Si, L. Natural products targeting glycolysis in cancer. Front. Pharmacol. 2022, 13, 1036502. [Google Scholar] [CrossRef]
- Zhao, M.; Wei, F.; Sun, G.; Wen, Y.; Xiang, J.; Su, F.; Zhan, L.; Nian, Q.; Chen, Y.; Zeng, J. Natural compounds targeting glycolysis as promising therapeutics for gastric cancer: A review. Front. Pharmacol. 2022, 13, 1004383. [Google Scholar] [CrossRef] [PubMed]
- Jin, L.; Kim, E.-Y.; Chung, T.-W.; Han, C.W.; Park, S.Y.; Han, J.H.; Bae, S.-J.; Lee, J.R.; Kim, Y.W.; Jang, S.B. Hemistepsin A suppresses colorectal cancer growth through inhibiting pyruvate dehydrogenase kinase activity. Sci. Rep. 2020, 10, 21940. [Google Scholar] [CrossRef]
- Kwak, C.-H.; Lee, J.-H.; Kim, E.-Y.; Han, C.W.; Kim, K.-J.; Lee, H.; Cho, M.; Jang, S.B.; Kim, C.-H.; Chung, T.-W. Huzhangoside A suppresses tumor growth through inhibition of pyruvate dehydrogenase kinase activity. Cancers 2019, 11, 712. [Google Scholar] [CrossRef]
- Kwak, C.-H.; Jin, L.; Han, J.H.; Han, C.W.; Kim, E.; Cho, M.; Chung, T.-W.; Bae, S.-J.; Jang, S.B.; Ha, K.-T. Ilimaquinone induces the apoptotic cell death of cancer cells by reducing pyruvate dehydrogenase kinase 1 activity. Int. J. Mol. Sci. 2020, 21, 6021. [Google Scholar] [CrossRef]
- Yuan, M.; Huang, L.-L.; Chen, J.-H.; Wu, J.; Xu, Q. The emerging treatment landscape of targeted therapy in non-small-cell lung cancer. Signal Transduct. Target. Ther. 2019, 4, 61. [Google Scholar] [CrossRef]
- Araghi, M.; Mannani, R.; Heidarnejad maleki, A.; Hamidi, A.; Rostami, S.; Safa, S.H.; Faramarzi, F.; Khorasani, S.; Alimohammadi, M.; Tahmasebi, S. Recent advances in non-small cell lung cancer targeted therapy; an update review. Cancer Cell Int. 2023, 23, 162. [Google Scholar] [CrossRef] [PubMed]
- Chan, B.A.; Hughes, B.G. Targeted therapy for non-small cell lung cancer: Current standards and the promise of the future. Transl. Lung Cancer Res. 2015, 4, 36–54. [Google Scholar] [PubMed]
- Ettinger, D.S.; Wood, D.E.; Aisner, D.L.; Akerley, W.; Bauman, J.R.; Bharat, A.; Bruno, D.S.; Chang, J.Y.; Chirieac, L.R.; D’Amico, T.A. Non–small cell lung cancer, version 3.2022, NCCN clinical practice guidelines in oncology. J. Natl. Compr. Cancer Netw. 2022, 20, 497–530. [Google Scholar] [CrossRef] [PubMed]
- Dungo, R.T.; Keating, G.M. Afatinib: First global approval. Drugs 2013, 73, 1503–1515. [Google Scholar] [CrossRef] [PubMed]
- Shirley, M. Dacomitinib: First global approval. Drugs 2018, 78, 1947–1953. [Google Scholar] [CrossRef] [PubMed]
- Cohen, M.H.; Johnson, J.R.; Chattopadhyay, S.; Tang, S.; Justice, R.; Sridhara, R.; Pazdur, R. Approval summary: Erlotinib maintenance therapy of advanced/metastatic non-small cell lung cancer (NSCLC). Oncologist 2010, 15, 1344–1351. [Google Scholar] [CrossRef] [PubMed]
- Kazandjian, D.; Blumenthal, G.M.; Yuan, W.; He, K.; Keegan, P.; Pazdur, R. FDA approval of gefitinib for the treatment of patients with metastatic EGFR mutation–positive non–small cell lung cancer. Clin. Cancer Res. 2016, 22, 1307–1312. [Google Scholar] [CrossRef]
- Ramalingam, S.S.; Yang, J.; Lee, C.K.; Kurata, T.; Kim, D.-W.; John, T.; Nogami, N.; Ohe, Y.; Mann, H.; Rukazenkov, Y. Osimertinib as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer. J. Clin. Oncol. 2018, 36, 841–849. [Google Scholar] [CrossRef]
- Park, K.; Haura, E.B.; Leighl, N.B.; Mitchell, P.; Shu, C.A.; Girard, N.; Viteri, S.; Han, J.Y.; Kim, S.W.; Lee, C.K.; et al. Amivantamab in EGFR Exon 20 Insertion-Mutated Non-Small-Cell Lung Cancer Progressing on Platinum Chemotherapy: Initial Results From the CHRYSALIS Phase I Study. J. Clin. Oncol. 2021, 39, 3391–3402. [Google Scholar] [CrossRef]
- Herden, M.; Waller, C.F. Alectinib. Recent Results Cancer Res. 2018, 211, 247–256. [Google Scholar]
- Markham, A. Brigatinib: First global approval. Drugs 2017, 77, 1131–1135. [Google Scholar] [CrossRef] [PubMed]
- Vansteenkiste, J.F.; Van De Kerkhove, C.; Wauters, E.; Van Mol, P. Capmatinib for the treatment of non-small cell lung cancer. Expert Rev. Anticancer Ther. 2019, 19, 659–671. [Google Scholar] [CrossRef] [PubMed]
- Chuang, J.C.; Neal, J.W. Crizotinib as first line therapy for advanced ALK-positive non-small cell lung cancers. Transl. Lung Cancer Res. 2015, 4, 639. [Google Scholar] [PubMed]
- Shaw, A.T.; Yasothan, U.; Kirkpatrick, P. Crizotinib. Nat. Rev. Drug Discov. 2011, 10, 897–898. [Google Scholar] [CrossRef] [PubMed]
- Sartore-Bianchi, A.; Pizzutilo, E.G.; Marrapese, G.; Tosi, F.; Cerea, G.; Siena, S. Entrectinib for the treatment of metastatic NSCLC: Safety and efficacy. Expert Rev. Anticancer Ther. 2020, 20, 333–341. [Google Scholar] [CrossRef] [PubMed]
- Scott, L.J. Larotrectinib: First global approval. Drugs 2019, 79, 201–206. [Google Scholar] [CrossRef] [PubMed]
- Shaw, A.T.; Bauer, T.M.; de Marinis, F.; Felip, E.; Goto, Y.; Liu, G.; Mazieres, J.; Kim, D.-W.; Mok, T.; Polli, A. First-line lorlatinib or crizotinib in advanced ALK-positive lung cancer. N. Engl. J. Med. 2020, 383, 2018–2029. [Google Scholar] [CrossRef]
- Markham, A. Pralsetinib: First approval. Drugs 2020, 80, 1865–1870. [Google Scholar] [CrossRef]
- Markham, A. Selpercatinib: First approval. Drugs 2020, 80, 1119–1124. [Google Scholar] [CrossRef]
- Paik, P.K.; Felip, E.; Veillon, R.; Sakai, H.; Cortot, A.B.; Garassino, M.C.; Mazieres, J.; Viteri, S.; Senellart, H.; Van Meerbeeck, J. Tepotinib in non–small-cell lung cancer with MET exon 14 skipping mutations. N. Engl. J. Med. 2020, 383, 931–943. [Google Scholar] [CrossRef]
- Nakajima, E.C.; Drezner, N.; Li, X.; Mishra-Kalyani, P.S.; Liu, Y.; Zhao, H.; Bi, Y.; Liu, J.; Rahman, A.; Wearne, E.; et al. FDA Approval Summary: Sotorasib for KRAS G12C-Mutated Metastatic NSCLC. Clin. Cancer Res. 2022, 28, 1482–1486. [Google Scholar] [CrossRef]
- Odogwu, L.; Mathieu, L.; Blumenthal, G.; Larkins, E.; Goldberg, K.B.; Griffin, N.; Bijwaard, K.; Lee, E.Y.; Philip, R.; Jiang, X. FDA approval summary: Dabrafenib and trametinib for the treatment of metastatic non-small cell lung cancers harboring BRAF V600E mutations. Oncologist 2018, 23, 740–745. [Google Scholar] [CrossRef] [PubMed]
- Akinboro, O.; Larkins, E.; Pai-Scherf, L.H.; Mathieu, L.N.; Ren, Y.; Cheng, J.; Fiero, M.H.; Fu, W.; Bi, Y.; Kalavar, S. FDA Approval summary: Pembrolizumab, atezolizumab, and cemiplimab-rwlc as single agents for first-line treatment of Advanced/Metastatic PD-L1–high NSCLC. Clin. Cancer Res. 2022, 28, 2221–2228. [Google Scholar] [CrossRef] [PubMed]
- Cohen, M.H.; Gootenberg, J.; Keegan, P.; Pazdur, R. FDA drug approval summary: Bevacizumab (Avastin®) plus carboplatin and paclitaxel as first-line treatment of advanced/metastatic recurrent nonsquamous non-small cell lung cancer. Oncologist 2007, 12, 713–718. [Google Scholar] [CrossRef] [PubMed]
- Vellanki, P.J.; Mulkey, F.; Jaigirdar, A.A.; Rodriguez, L.; Wang, Y.; Xu, Y.; Zhao, H.; Liu, J.; Howe, G.; Wang, J. FDA Approval Summary: Nivolumab with Ipilimumab and Chemotherapy for Metastatic Non–small Cell Lung Cancer, A Collaborative Project Orbis ReviewFDA Approval: Nivolumab with Ipilimumab and Chemotherapy. Clin. Cancer Res. 2021, 27, 3522–3527. [Google Scholar] [CrossRef]
- Kazandjian, D.; Suzman, D.L.; Blumenthal, G.; Mushti, S.; He, K.; Libeg, M.; Keegan, P.; Pazdur, R. FDA approval summary: Nivolumab for the treatment of metastatic non-small cell lung cancer with progression on or after platinum-based chemotherapy. Oncologist 2016, 21, 634–642. [Google Scholar] [CrossRef]
- Reck, M. Pembrolizumab as first-line therapy for metastatic non-small-cell lung cancer. Immunotherapy 2018, 10, 93–105. [Google Scholar] [CrossRef]
- Martinelli, E.; De Palma, R.; Orditura, M.; De Vita, F.; Ciardiello, F. Anti-epidermal growth factor receptor monoclonal antibodies in cancer therapy. Clin. Exp. Immunol. 2009, 158, 1–9. [Google Scholar] [CrossRef]
- Garnock-Jones, K.P. Necitumumab: First Global Approval. Drugs 2016, 76, 283–289. [Google Scholar] [CrossRef]
- Herbst, R.S. Review of epidermal growth factor receptor biology. Int. J. Radiat. Oncol. Biol. Phys. 2004, 59, S21–S26. [Google Scholar] [CrossRef]
- Schlessinger, J. Cell signaling by receptor tyrosine kinases. Cell 2000, 103, 211–225. [Google Scholar] [CrossRef] [PubMed]
- Yarden, Y. The EGFR family and its ligands in human cancer: Signalling mechanisms and therapeutic opportunities. Eur. J. Cancer 2001, 37, 3–8. [Google Scholar] [CrossRef] [PubMed]
- Ciardiello, F.; Tortora, G. EGFR antagonists in cancer treatment. N. Engl. J. Med. 2008, 358, 1160–1174. [Google Scholar] [CrossRef] [PubMed]
- Shah, R.; Lester, J.F. Tyrosine Kinase Inhibitors for the Treatment of EGFR Mutation-Positive Non-Small-Cell Lung Cancer: A Clash of the Generations. Clin. Lung Cancer 2020, 21, e216–e228. [Google Scholar] [CrossRef]
- Wieduwilt, M.; Moasser, M. The epidermal growth factor receptor family: Biology driving targeted therapeutics. Cell. Mol. Life Sci. 2008, 65, 1566–1584. [Google Scholar] [CrossRef] [PubMed]
- Burgess, A.W.; Cho, H.-S.; Eigenbrot, C.; Ferguson, K.M.; Garrett, T.P.; Leahy, D.J.; Lemmon, M.A.; Sliwkowski, M.X.; Ward, C.W.; Yokoyama, S. An open-and-shut case? Recent insights into the activation of EGF/ErbB receptors. Mol. Cell 2003, 12, 541–552. [Google Scholar] [CrossRef]
- Schlessinger, J. Ligand-induced, receptor-mediated dimerization and activation of EGF receptor. Cell 2002, 110, 669–672. [Google Scholar] [CrossRef]
- Zhang, X.; Gureasko, J.; Shen, K.; Cole, P.A.; Kuriyan, J. An allosteric mechanism for activation of the kinase domain of epidermal growth factor receptor. Cell 2006, 125, 1137–1149. [Google Scholar] [CrossRef]
- Siegelin, M.D.; Borczuk, A.C. Epidermal growth factor receptor mutations in lung adenocarcinoma. Lab. Investig. 2014, 94, 129–137. [Google Scholar] [CrossRef]
- Huang, S.-F.; Cheng, S.-D.; Chien, H.-T.; Liao, C.-T.; Chen, I.-H.; Wang, H.-M.; Chuang, W.-Y.; Wang, C.-Y.; Hsieh, L.-L. Relationship between epidermal growth factor receptor gene copy number and protein expression in oral cavity squamous cell carcinoma. Oral Oncol. 2012, 48, 67–72. [Google Scholar] [CrossRef]
- Sharma, S.V.; Bell, D.W.; Settleman, J.; Haber, D.A. Epidermal growth factor receptor mutations in lung cancer. Nat. Rev. Cancer 2007, 7, 169–181. [Google Scholar] [CrossRef] [PubMed]
- Sullivan, I.; Planchard, D. Next-Generation EGFR Tyrosine Kinase Inhibitors for Treating EGFR-Mutant Lung Cancer beyond First Line. Front. Med. 2016, 3, 76. [Google Scholar] [CrossRef]
- Lynch, T.J.; Bell, D.W.; Sordella, R.; Gurubhagavatula, S.; Okimoto, R.A.; Brannigan, B.W.; Harris, P.L.; Haserlat, S.M.; Supko, J.G.; Haluska, F.G. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non–small-cell lung cancer to gefitinib. N. Engl. J. Med. 2004, 350, 2129–2139. [Google Scholar] [CrossRef] [PubMed]
- Chen, Y.R.; Fu, Y.N.; Lin, C.H.; Yang, S.T.; Hu, S.F.; Chen, Y.T.; Tsai, S.F.; Huang, S.F. Distinctive activation patterns in constitutively active and gefitinib-sensitive EGFR mutants. Oncogene 2006, 25, 1205–1215. [Google Scholar] [CrossRef] [PubMed]
- Kancha, R.K.; von Bubnoff, N.; Peschel, C.; Duyster, J. Functional analysis of epidermal growth factor receptor (EGFR) mutations and potential implications for EGFR targeted therapy. Clin. Cancer Res. 2009, 15, 460–467. [Google Scholar] [CrossRef] [PubMed]
- Chang, J.W.; Chang, C.F.; Huang, C.Y.; Yang, C.T.; Kuo, C.S.; Fang, Y.F.; Hsu, P.C.; Wu, C.E. The survival after discontinuation of EGFR-TKIs due to intolerable adverse events in patients with EGFR-mutated non-small cell lung cancer. Thorac. Cancer 2023, 14, 348–356. [Google Scholar] [CrossRef] [PubMed]
- Yu, H.A.; Arcila, M.E.; Rekhtman, N.; Sima, C.S.; Zakowski, M.F.; Pao, W.; Kris, M.G.; Miller, V.A.; Ladanyi, M.; Riely, G.J. Analysis of Tumor Specimens at the Time of Acquired Resistance to EGFR-TKI Therapy in 155 Patients with EGFR-Mutant Lung CancersMechanisms of Acquired Resistance to EGFR-TKI Therapy. Clin. Cancer Res. 2013, 19, 2240–2247. [Google Scholar] [CrossRef]
- Campo, M.; Gerber, D.; Gainor, J.F.; Heist, R.S.; Temel, J.S.; Shaw, A.T.; Fidias, P.; Muzikansky, A.; Engelman, J.A.; Sequist, L.V. Acquired resistance to first-line afatinib and the challenges of prearranged progression biopsies. J. Thorac. Oncol. 2016, 11, 2022–2026. [Google Scholar] [CrossRef]
- Wu, Y.L.; Cheng, Y.; Zhou, X.; Lee, K.H.; Nakagawa, K.; Niho, S.; Tsuji, F.; Linke, R.; Rosell, R.; Corral, J.; et al. Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): A randomised, open-label, phase 3 trial. Lancet Oncoll 2017, 18, 1454–1466. [Google Scholar] [CrossRef]
- Kobayashi, Y.; Fujino, T.; Nishino, M.; Koga, T.; Chiba, M.; Sesumi, Y.; Ohara, S.; Shimoji, M.; Tomizawa, K.; Takemoto, T.; et al. EGFR T790M and C797S Mutations as Mechanisms of Acquired Resistance to Dacomitinib. J. Thorac. Oncol. 2018, 13, 727–731. [Google Scholar] [CrossRef]
- Asahina, H.; Tanaka, K.; Morita, S.; Maemondo, M.; Seike, M.; Okamoto, I.; Oizumi, S.; Kagamu, H.; Takahashi, K.; Kikuchi, T. A Phase II Study of Osimertinib Combined With Platinum Plus Pemetrexed in Patients With EGFR-Mutated Advanced Non–Small-cell Lung Cancer: The OPAL Study (NEJ032C/LOGIK1801). Clin. Lung Cancer 2021, 22, 147–151. [Google Scholar] [CrossRef]
- Shi, K.; Wang, G.; Pei, J.; Zhang, J.; Wang, J.; Ouyang, L.; Wang, Y.; Li, W. Emerging strategies to overcome resistance to third-generation EGFR inhibitors. J. Hematol. Oncol. 2022, 15, 94. [Google Scholar] [CrossRef] [PubMed]
- Khozin, S.; Blumenthal, G.M.; Jiang, X.; He, K.; Boyd, K.; Murgo, A.; Justice, R.; Keegan, P.; Pazdur, R. US Food and Drug Administration approval summary: Erlotinib for the first-line treatment of metastatic non-small cell lung cancer with epidermal growth factor receptor exon 19 deletions or exon 21 (L858R) substitution mutations. Oncologist 2014, 19, 774–779. [Google Scholar] [CrossRef] [PubMed]
- Markham, A. Mobocertinib: First Approval. Drugs 2021, 81, 2069–2074. [Google Scholar] [CrossRef] [PubMed]
- Greig, S.L. Osimertinib: First global approval. Drugs 2016, 76, 263–273. [Google Scholar] [CrossRef] [PubMed]
- Food and Drug Administration. FDA Approves Osimertinib for First-Line Treatment of Metastatic NSCLC with Most Common EGFR Mutations; Food and Drug Administration: White Oak, MD, USA, 2018.
- Koch, A.L.; Vellanki, P.J.; Drezner, N.; Li, X.; Mishra-Kalyani, P.S.; Shen, Y.L.; Xia, H.; Li, Y.; Liu, J.; Zirkelbach, J.F. FDA Approval Summary: Osimertinib for Adjuvant Treatment of Surgically Resected Non–Small Cell Lung Cancer, a Collaborative Project Orbis ReviewFDA Approval: Adjuvant Osimertinib for EGFR-Mutated NSCLC. Clin. Cancer Res. 2021, 27, 6638–6643. [Google Scholar] [CrossRef] [PubMed]
- Vander Heiden, M.G.; Cantley, L.C.; Thompson, C.B. Understanding the Warburg effect: The metabolic requirements of cell proliferation. Science 2009, 324, 1029–1033. [Google Scholar] [CrossRef]
- Warburg, O. On the origin of cancer cells. Science 1956, 123, 309–314. [Google Scholar] [CrossRef]
- Pelicano, H.; Martin, D.; Xu, R.; Huang, P. Glycolysis inhibition for anticancer treatment. Oncogene 2006, 25, 4633. [Google Scholar] [CrossRef]
- Gatenby, R.A.; Gillies, R.J. Why do cancers have high aerobic glycolysis? Nat. Rev. Cancer 2004, 4, 891–899. [Google Scholar] [CrossRef]
- Phaniendra, A.; Jestadi, D.B.; Periyasamy, L. Free radicals: Properties, sources, targets, and their implication in various diseases. Indian J. Clin. Biochem. 2015, 30, 11–26. [Google Scholar] [CrossRef] [PubMed]
- Chen, Y.; Shi, J.; Wang, X.; Zhou, L.; Wang, Q.; Xie, Y.; Peng, C.; Kuang, L.; Yang, D.; Yang, J.; et al. An antioxidant feedforward cycle coordinated by linker histone variant H1.2 and NRF2 that drives nonsmall cell lung cancer progression. Proc. Natl. Acad. Sci. USA 2023, 120, e2306288120. [Google Scholar] [CrossRef] [PubMed]
- Cheng, H.; Shcherba, M.; Pendurti, G.; Liang, Y.; Piperdi, B.; Perez-Soler, R. Targeting the PI3K/AKT/mTOR pathway: Potential for lung cancer treatment. Lung Cancer Manag. 2014, 3, 67–75. [Google Scholar] [CrossRef] [PubMed]
- Burgess, J.T.; Rose, M.; Boucher, D.; Plowman, J.; Molloy, C.; Fisher, M.; O’Leary, C.; Richard, D.J.; O’Byrne, K.J.; Bolderson, E. The Therapeutic Potential of DNA Damage Repair Pathways and Genomic Stability in Lung Cancer. Front. Oncol. 2020, 10, 1256. [Google Scholar] [CrossRef] [PubMed]
- Shi, Y.; Fan, S.; Wu, M.; Zuo, Z.; Li, X.; Jiang, L.; Shen, Q.; Xu, P.; Zeng, L.; Zhou, Y.; et al. YTHDF1 links hypoxia adaptation and non-small cell lung cancer progression. Nat. Commun. 2019, 10, 4892. [Google Scholar] [CrossRef] [PubMed]
- Apicella, M.; Giannoni, E.; Fiore, S.; Ferrari, K.J.; Fernández-Pérez, D.; Isella, C.; Granchi, C.; Minutolo, F.; Sottile, A.; Comoglio, P.M. Increased lactate secretion by cancer cells sustains non-cell-autonomous adaptive resistance to MET and EGFR targeted therapies. Cell Metab. 2018, 28, 848–865.e6. [Google Scholar] [CrossRef]
- Keam, B.; Lee, S.J.; Kim, T.M.; Paeng, J.C.; Lee, S.H.; Kim, D.W.; Jeon, Y.K.; Chung, D.H.; Kang, K.W.; Chung, J.K.; et al. Total Lesion Glycolysis in Positron Emission Tomography Can Predict Gefitinib Outcomes in Non-Small-Cell Lung Cancer with Activating EGFR Mutation. J. Thorac. Oncol. 2015, 10, 1189–1194. [Google Scholar] [CrossRef]
- Suzuki, S.; Okada, M.; Takeda, H.; Kuramoto, K.; Sanomachi, T.; Togashi, K.; Seino, S.; Yamamoto, M.; Yoshioka, T.; Kitanaka, C. Involvement of GLUT1-mediated glucose transport and metabolism in gefitinib resistance of non-small-cell lung cancer cells. Oncotarget 2018, 9, 32667–32679. [Google Scholar] [CrossRef]
- Wang, J.; Ye, C.; Chen, C.; Xiong, H.; Xie, B.; Zhou, J.; Chen, Y.; Zheng, S.; Wang, L. Glucose transporter GLUT1 expression and clinical outcome in solid tumors: A systematic review and meta-analysis. Oncotarget 2017, 8, 16875–16886. [Google Scholar] [CrossRef]
- Kim, S.M.; Yun, M.R.; Hong, Y.K.; Solca, F.; Kim, J.H.; Kim, H.J.; Cho, B.C. Glycolysis inhibition sensitizes non-small cell lung cancer with T790M mutation to irreversible EGFR inhibitors via translational suppression of Mcl-1 by AMPK activation. Mol. Cancer Ther. 2013, 12, 2145–2156. [Google Scholar] [CrossRef]
- Ciscato, F.; Ferrone, L.; Masgras, I.; Laquatra, C.; Rasola, A. Hexokinase 2 in Cancer: A Prima Donna Playing Multiple Characters. Int. J. Mol. Sci. 2021, 22, 4716. [Google Scholar] [CrossRef] [PubMed]
- Israelsen, W.J.; Vander Heiden, M.G. Pyruvate kinase: Function, regulation and role in cancer. Semin. Cell Dev. Biol. 2015, 43, 43–51. [Google Scholar] [CrossRef]
- Li, Q.; Zhang, D.; Chen, X.; He, L.; Li, T.; Xu, X.; Li, M. Nuclear PKM2 contributes to gefitinib resistance via upregulation of STAT3 activation in colorectal cancer. Sci. Rep. 2015, 5, 16082. [Google Scholar] [CrossRef] [PubMed]
- Stacpoole, P.W. Therapeutic Targeting of the Pyruvate Dehydrogenase Complex/Pyruvate Dehydrogenase Kinase (PDC/PDK) Axis in Cancer. J. Natl. Cancer Inst. 2017, 109. [Google Scholar] [CrossRef] [PubMed]
- Han, J.H.; Lee, E.J.; Park, W.; Ha, K.T.; Chung, H.S. Natural compounds as lactate dehydrogenase inhibitors: Potential therapeutics for lactate dehydrogenase inhibitors-related diseases. Front. Pharmacol. 2023, 14, 1275000. [Google Scholar] [CrossRef] [PubMed]
- Xu, J.Q.; Fu, Y.L.; Zhang, J.; Zhang, K.Y.; Ma, J.; Tang, J.Y.; Zhang, Z.W.; Zhou, Z.Y. Targeting glycolysis in non-small cell lung cancer: Promises and challenges. Front. Pharmacol. 2022, 13, 1037341. [Google Scholar] [CrossRef] [PubMed]
- Lin, C.; Chen, H.; Han, R.; Li, L.; Lu, C.; Hao, S.; Wang, Y.; He, Y. Hexokinases II-mediated glycolysis governs susceptibility to crizotinib in ALK-positive non-small cell lung cancer. Thorac. Cancer 2021, 12, 3184–3193. [Google Scholar] [CrossRef]
- Yang, Z.; Zhang, S.L.; Hu, X.; Tam, K.Y. Inhibition of pyruvate dehydrogenase kinase 1 enhances the anti-cancer effect of EGFR tyrosine kinase inhibitors in non-small cell lung cancer. Eur. J. Pharmacol. 2018, 838, 41–52. [Google Scholar] [CrossRef]
- Ma, R.; Li, X.; Gong, S.; Ge, X.; Zhu, T.; Ge, X.; Weng, L.; Tao, Q.; Guo, J. Dual Roles of Lactate in EGFR-TKI-Resistant Lung Cancer by Targeting GPR81 and MCT1. J. Oncol. 2022, 2022, 3425841. [Google Scholar] [CrossRef]
- Jeoung, N.H. Pyruvate dehydrogenase kinases: Therapeutic targets for diabetes and cancers. Diabetes Metab. J. 2015, 39, 188. [Google Scholar] [CrossRef]
- Schell, J.C.; Olson, K.A.; Jiang, L.; Hawkins, A.J.; Van Vranken, J.G.; Xie, J.; Egnatchik, R.A.; Earl, E.G.; DeBerardinis, R.J.; Rutter, J. A role for the mitochondrial pyruvate carrier as a repressor of the Warburg effect and colon cancer cell growth. Mol. Cell 2014, 56, 400–413. [Google Scholar] [CrossRef]
- Liu, T.; Yin, H. PDK1 promotes tumor cell proliferation and migration by enhancing the Warburg effect in non-small cell lung cancer. Oncol. Rep. 2017, 37, 193–200. [Google Scholar] [CrossRef] [PubMed]
- Papandreou, I.; Cairns, R.A.; Fontana, L.; Lim, A.L.; Denko, N.C. HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption. Cell Metab. 2006, 3, 187–197. [Google Scholar] [CrossRef] [PubMed]
- Viale, A.; Corti, D.; Draetta, G.F. Tumors and Mitochondrial Respiration: A Neglected ConnectionMitochondrial Role in Tumor Progression. Cancer Res. 2015, 75, 3687–3691. [Google Scholar] [CrossRef] [PubMed]
- Park, W.; Wei, S.; Kim, B.S.; Kim, B.; Bae, S.J.; Chae, Y.C.; Ryu, D.; Ha, K.T. Diversity and complexity of cell death: A historical review. Exp. Mol. Med. 2023, 55, 1573–1594. [Google Scholar] [CrossRef] [PubMed]
- Steussy, C.N.; Popov, K.M.; Bowker-Kinley, M.M.; Sloan, R.B.; Harris, R.A.; Hamilton, J.A. Structure of pyruvate dehydrogenase kinase: Novel folding pattern for a serine protein kinase. J. Biol. Chem. 2001, 276, 37443–37450. [Google Scholar] [CrossRef]
- Michelakis, E.; Webster, L.; Mackey, J. Dichloroacetate (DCA) as a potential metabolic-targeting therapy for cancer. Br. J. Cancer 2008, 99, 989–994. [Google Scholar] [CrossRef]
- Yang, Z.; Tam, K.Y. Anti-cancer synergy of dichloroacetate and EGFR tyrosine kinase inhibitors in NSCLC cell lines. Eur. J. Pharmacol. 2016, 789, 458–467. [Google Scholar] [CrossRef]
- Dyrstad, S.E.; Lotsberg, M.L.; Tan, T.Z.; Pettersen, I.K.; Hjellbrekke, S.; Tusubira, D.; Engelsen, A.S.; Daubon, T.; Mourier, A.; Thiery, J.P. Blocking aerobic glycolysis by targeting pyruvate dehydrogenase kinase in combination with EGFR TKI and ionizing radiation increases therapeutic effect in non-small cell lung cancer cells. Cancers 2021, 13, 941. [Google Scholar] [CrossRef]
- Xu, H.; He, Y.; Ma, J.; Zhao, Y.; Liu, Y.; Sun, L.; Su, J. Inhibition of pyruvate dehydrogenase kinase-1 by dicoumarol enhances the sensitivity of hepatocellular carcinoma cells to oxaliplatin via metabolic reprogramming. Int. J. Oncol. 2020, 57, 733–742. [Google Scholar] [CrossRef]
- Tambe, Y.; Terado, T.; Kim, C.J.; Mukaisho, K.I.; Yoshida, S.; Sugihara, H.; Tanaka, H.; Chida, J.; Kido, H.; Yamaji, K. Antitumor activity of potent pyruvate dehydrogenase kinase 4 inhibitors from plants in pancreatic cancer. Mol. Carcinog. 2019, 58, 1726–1737. [Google Scholar] [CrossRef] [PubMed]
- Zheng, S.-Y.; Li, Y.; Jiang, D.; Zhao, J.; Ge, J.-F. Anticancer effect and apoptosis induction by quercetin in the human lung cancer cell line A-549. Mol. Med. Rep. 2012, 5, 822–826. [Google Scholar] [CrossRef] [PubMed]
- Chen, F.; Zhuang, M.; Zhong, C.; Peng, J.; Wang, X.; Li, J.; Chen, Z.; Huang, Y. Baicalein reverses hypoxia-induced 5-FU resistance in gastric cancer AGS cells through suppression of glycolysis and the PTEN/Akt/HIF-1alpha signaling pathway. Oncol. Rep. 2015, 33, 457–463. [Google Scholar] [CrossRef] [PubMed]
- Tao, H.; Ding, X.; Wu, J.; Liu, S.; Sun, W.; Nie, M.; Pan, X.; Zou, X. beta-Asarone Increases Chemosensitivity by Inhibiting Tumor Glycolysis in Gastric Cancer. Evid. Based Complement Altern. Med. 2020, 2020, 6981520. [Google Scholar] [CrossRef] [PubMed]
- Wang, P.; Jin, J.M.; Liang, X.H.; Yu, M.Z.; Yang, C.; Huang, F.; Wu, H.; Zhang, B.B.; Fei, X.Y.; Wang, Z.T.; et al. Helichrysetin inhibits gastric cancer growth by targeting c-Myc/PDHK1 axis-mediated energy metabolism reprogramming. Acta Pharmacol. Sin. 2022, 43, 1581–1593. [Google Scholar] [CrossRef]
- Jiao, L.; Wang, S.; Zheng, Y.; Wang, N.; Yang, B.; Wang, D.; Yang, D.; Mei, W.; Zhao, Z.; Wang, Z. Betulinic acid suppresses breast cancer aerobic glycolysis via caveolin-1/NF-kappaB/c-Myc pathway. Biochem. Pharmacol. 2019, 161, 149–162. [Google Scholar] [CrossRef]
- Jin, J.; Qiu, S.; Wang, P.; Liang, X.; Huang, F.; Wu, H.; Zhang, B.; Zhang, W.; Tian, X.; Xu, R.; et al. Cardamonin inhibits breast cancer growth by repressing HIF-1alpha-dependent metabolic reprogramming. J. Exp. Clin. Cancer Res. 2019, 38, 377. [Google Scholar] [CrossRef]
- Aicher, T.D.; Damon, R.E.; Koletar, J.; Vinluan, C.C.; Brand, L.J.; Gao, J.; Shetty, S.S.; Kaplan, E.L.; Mann, W.R. Triterpene and diterpene inhibitors of pyruvate dehydrogenase kinase (PDK). Bioorganic Med. Chem. Lett. 1999, 9, 2223–2228. [Google Scholar] [CrossRef]
- Ha, K.-T. Composition for Preventing or Treating Cancer, and Containing Otobaphenol as Active Component. WO2018026210A1, 8 February 2018. [Google Scholar]
- Dahiya, R.; Mohammad, T.; Roy, S.; Anwar, S.; Gupta, P.; Haque, A.; Khan, P.; Kazim, S.N.; Islam, A.; Ahmad, F. Investigation of inhibitory potential of quercetin to the pyruvate dehydrogenase kinase 3: Towards implications in anticancer therapy. Int. J. Biol. Macromol. 2019, 136, 1076–1085. [Google Scholar] [CrossRef]
- Fantin, V.R.; St-Pierre, J.; Leder, P. Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance. Cancer Cell 2006, 9, 425–434. [Google Scholar] [CrossRef]
- Livesey, A.; Garty, F.; Shipman, A.; Shipman, K. Lactate dehydrogenase in dermatology practice. Clin. Exp. Dermatol. 2020, 45, 539–543. [Google Scholar] [CrossRef] [PubMed]
- Hols, P.; Ramos, A.; Hugenholtz, J.; Delcour, J.; de Vos, W.M.; Santos, H.; Kleerebezem, M. Acetate utilization in Lactococcus lactis deficient in lactate dehydrogenase: A rescue pathway for maintaining redox balance. J. Bacteriol. 1999, 181, 5521–5526. [Google Scholar] [CrossRef] [PubMed]
- Holmes, R.S.; Goldberg, E. Computational analyses of mammalian lactate dehydrogenases: Human, mouse, opossum and platypus LDHs. Comput. Biol. Chem. 2009, 33, 379–385. [Google Scholar] [CrossRef] [PubMed]
- Urbańska, K.; Orzechowski, A. Unappreciated Role of LDHA and LDHB to Control Apoptosis and Autophagy in Tumor Cells. Int. J. Mol. Sci. 2019, 20, 2085. [Google Scholar] [CrossRef] [PubMed]
- Kane, D.A. Lactate oxidation at the mitochondria: A lactate-malate-aspartate shuttle at work. Front. Neurosci. 2014, 8, 366. [Google Scholar] [CrossRef] [PubMed]
- Read, J.; Winter, V.; Eszes, C.; Sessions, R.; Brady, R. Structural basis for altered activity of M- and H-isozyme forms of human lactate dehydrogenase. Proteins Struct. Funct. Bioinform. 2001, 43, 175–185. [Google Scholar] [CrossRef]
- Imagawa, T.; Yamamoto, E.; Sawada, M.; Okamoto, M.; Uehara, M. Expression of lactate dehydrogenase-A and-B messenger ribonucleic acids in chick glycogen body. Poult. Sci. 2006, 85, 1232–1238. [Google Scholar] [CrossRef]
- Feng, Y.; Xiong, Y.; Qiao, T.; Li, X.; Jia, L.; Han, Y. Lactate dehydrogenase A: A key player in carcinogenesis and potential target in cancer therapy. Cancer Med. 2018, 7, 6124–6136. [Google Scholar] [CrossRef]
- Klein, R.; Nagy, O.; Tóthová, C.; Chovanová, F. Clinical and Diagnostic Significance of Lactate Dehydrogenase and Its Isoenzymes in Animals. Vet. Med. Int. 2020, 2020, 5346483. [Google Scholar] [CrossRef]
- Yang, C.; Pan, R.Y.; Guan, F.; Yuan, Z. Lactate metabolism in neurodegenerative diseases. Neural Regen Res. 2024, 19, 69–74. [Google Scholar] [CrossRef]
- Zhu, W.; Ma, Y.; Guo, W.; Lu, J.; Li, X.; Wu, J.; Qin, P.; Zhu, C.; Zhang, Q. Serum Level of Lactate Dehydrogenase is Associated with Cardiovascular Disease Risk as Determined by the Framingham Risk Score and Arterial Stiffness in a Health-Examined Population in China. Int. J. Gen. Med. 2022, 15, 11–17. [Google Scholar] [CrossRef] [PubMed]
- Chen, Z.; Lu, W.; Garcia-Prieto, C.; Huang, P. The Warburg effect and its cancer therapeutic implications. J. Bioenerg. Biomembr. 2007, 39, 267–274. [Google Scholar] [CrossRef]
- Mishra, D.; Banerjee, D. Lactate Dehydrogenases as Metabolic Links between Tumor and Stroma in the Tumor Microenvironment. Cancers 2019, 11, 750. [Google Scholar] [CrossRef] [PubMed]
- Inomata, M.; Hayashi, R.; Tanaka, H.; Shimokawa, K.; Tokui, K.; Taka, C.; Okazawa, S.; Kambara, K.; Ichikawa, T.; Yamada, T.; et al. Elevated levels of plasma lactate dehydrogenase is an unfavorable prognostic factor in patients with epidermal growth factor receptor mutation-positive non-small cell lung cancer, receiving treatment with gefitinib or erlotinib. Mol. Clin. Oncol. 2016, 4, 774–778. [Google Scholar] [CrossRef]
- Gong, T.; Liu, J.; Jiang, J.; Zhai, Y.F.; Wu, C.M.; Ma, C.; Wen, B.L.; Yan, X.Y.; Zhang, X.; Wang, D.M.; et al. The role of lactate deshydrogenase levels on non-small cell lung cancer prognosis: A meta-analysis. Cell. Mol. Biol. (Noisy-Le-Grand) 2019, 65, 89–93. [Google Scholar] [CrossRef] [PubMed]
- Korga, A.; Ostrowska, M.; Jozefczyk, A.; Iwan, M.; Wojcik, R.; Zgorka, G.; Herbet, M.; Vilarrubla, G.G.; Dudka, J. Apigenin and hesperidin augment the toxic effect of doxorubicin against HepG2 cells. BMC Pharmacol. Toxicol. 2019, 20, 22. [Google Scholar] [CrossRef] [PubMed]
- Zhu, N.; Li, J.; Li, Y.; Zhang, Y.; Du, Q.; Hao, P.; Li, J.; Cao, X.; Li, L. Berberine protects against simulated ischemia/reperfusion injury-induced H9C2 cardiomyocytes apoptosis in vitro and myocardial ischemia/reperfusion-induced apoptosis in vivo by regulating the mitophagy-mediated HIF-1α/BNIP3 pathway. Front. Pharmacol. 2020, 11, 367. [Google Scholar] [CrossRef] [PubMed]
- Hwang, Y.P.; Yun, H.J.; Choi, J.H.; Han, E.H.; Kim, H.G.; Song, G.Y.; Kwon, K.i.; Jeong, T.C.; Jeong, H.G. Suppression of EGF-induced tumor cell migration and matrix metalloproteinase-9 expression by capsaicin via the inhibition of EGFR-mediated FAK/Akt, PKC/Raf/ERK, p38 MAPK, and AP-1 signaling. Mol. Nutr. Food Res. 2011, 55, 594–605. [Google Scholar] [CrossRef]
- Chen, X.Q.; Hu, T.; Han, Y.; Huang, W.; Yuan, H.B.; Zhang, Y.T.; Du, Y.; Jiang, Y.W. Preventive Effects of Catechins on Cardiovascular Disease. Molecules 2016, 21, 1759. [Google Scholar] [CrossRef]
- Wang, K.; Fan, H.; Chen, Q.; Ma, G.; Zhu, M.; Zhang, X.; Zhang, Y.; Yu, J. Curcumin inhibits aerobic glycolysis and induces mitochondrial-mediated apoptosis through hexokinase II in human colorectal cancer cells in vitro. Anticancer Drugs 2015, 26, 15–24. [Google Scholar] [CrossRef]
- Chen, P.; Huang, H.P.; Wang, Y.; Jin, J.; Long, W.G.; Chen, K.; Zhao, X.H.; Chen, C.G.; Li, J. Curcumin overcome primary gefitinib resistance in non-small-cell lung cancer cells through inducing autophagy-related cell death. J. Exp. Clin. Cancer Res. 2019, 38, 254. [Google Scholar] [CrossRef] [PubMed]
- Li, S.; Liu, Z.; Zhu, F.; Fan, X.; Wu, X.; Zhao, H.; Jiang, L. Curcumin lowers erlotinib resistance in non-small cell lung carcinoma cells with mutated EGF receptor. Oncol. Res. 2013, 21, 137–144. [Google Scholar] [CrossRef] [PubMed]
- Lu, Q.Y.; Zhang, L.; Yee, J.K.; Go, V.W.; Lee, W.N. Metabolic Consequences of LDHA inhibition by Epigallocatechin Gallate and Oxamate in MIA PaCa-2 Pancreatic Cancer Cells. Metabolomics 2015, 11, 71–80. [Google Scholar] [CrossRef] [PubMed]
- Zhang, X.; Zhang, H.; Tighiouart, M.; Lee, J.E.; Shin, H.J.; Khuri, F.R.; Yang, C.S.; Chen, Z.; Shin, D.M. Synergistic inhibition of head and neck tumor growth by green tea (−)-epigallocatechin-3-gallate and EGFR tyrosine kinase inhibitor. Int. J. Cancer 2008, 123, 1005–1014. [Google Scholar] [CrossRef] [PubMed]
- Haque, A.; Rahman, M.A.; Chen, Z.G.; Saba, N.F.; Khuri, F.R.; Shin, D.M.; Ruhul Amin, A.R. Combination of erlotinib and EGCG induces apoptosis of head and neck cancers through posttranscriptional regulation of Bim and Bcl-2. Apoptosis 2015, 20, 986–995. [Google Scholar] [CrossRef]
- Grosse, F.; Nasheuer, H.P.; Scholtissek, S.; Schomburg, U. Lactate dehydrogenase and glyceraldehyde-phosphate dehydrogenase are single-stranded DNA-binding proteins that affect the DNA-polymerase-alpha-primase complex. Eur. J. Biochem. 1986, 160, 459–467. [Google Scholar] [CrossRef] [PubMed]
- Fiume, L.; Vettraino, M.; Carnicelli, D.; Arfilli, V.; Di Stefano, G.; Brigotti, M. Galloflavin prevents the binding of lactate dehydrogenase A to single stranded DNA and inhibits RNA synthesis in cultured cells. Biochem. Biophys. Res. Commun. 2013, 430, 466–469. [Google Scholar] [CrossRef]
- Liu, X.; Pan, L.; Chen, P.; Zhu, Y. Leonurine improves ischemia-induced myocardial injury through antioxidative activity. Phytomedicine 2010, 17, 753–759. [Google Scholar] [CrossRef]
- Maurya, A.K.; Vinayak, M. Quercetin regresses Dalton’s lymphoma growth via suppression of PI3K/AKT signaling leading to upregulation of p53 and decrease in energy metabolism. Nutr. Cancer 2015, 67, 354–363. [Google Scholar] [CrossRef]
- Mlala, S.; Oyedeji, A.O.; Gondwe, M.; Oyedeji, O.O. Ursolic acid and its derivatives as bioactive agents. Molecules 2019, 24, 2751. [Google Scholar] [CrossRef]
- Wang, S.; Chang, X.; Zhang, J.; Li, J.; Wang, N.; Yang, B.; Pan, B.; Zheng, Y.; Wang, X.; Ou, H. Ursolic acid inhibits breast cancer metastasis by suppressing glycolytic metabolism via activating sp1/caveolin-1 signaling. Front. Oncol. 2021, 11, 745584. [Google Scholar] [CrossRef] [PubMed]
- Sikander, M.; Malik, S.; Chauhan, N.; Khan, P.; Kumari, S.; Kashyap, V.K.; Khan, S.; Ganju, A.; Halaweish, F.T.; Yallapu, M.M. Cucurbitacin D reprograms glucose metabolic network in prostate cancer. Cancers 2019, 11, 364. [Google Scholar] [CrossRef] [PubMed]
- Yar Saglam, A.; Alp, E.; Elmazoglu, Z.; Menevse, S. Treatment with cucurbitacin B alone and in combination with gefitinib induces cell cycle inhibition and apoptosis via EGFR and JAK/STAT pathway in human colorectal cancer cell lines. Hum. Exp. Toxicol. 2016, 35, 526–543. [Google Scholar] [CrossRef] [PubMed]
- Li, S.; Li, J.; Dai, W.; Zhang, Q.; Feng, J.; Wu, L.; Liu, T.; Yu, Q.; Xu, S.; Wang, W. Genistein suppresses aerobic glycolysis and induces hepatocellular carcinoma cell death. Br. J. Cancer 2017, 117, 1518–1528. [Google Scholar] [CrossRef] [PubMed]
- Keyhanmanesh, R.; Saadat, S.; Mohammadi, M.; Shahbazfar, A.A.; Fallahi, M. The protective effect of α-hederin, the active constituent of Nigella sativa, on lung inflammation and blood cytokines in ovalbumin sensitized Guinea pigs. Phytother. Res. 2015, 29, 1761–1767. [Google Scholar] [CrossRef]
- Fang, C.; Liu, Y.; Chen, L.; Luo, Y.; Cui, Y.; Zhang, N.; Liu, P.; Zhou, M.; Xie, Y. α-Hederin inhibits the growth of lung cancer A549 cells in vitro and in vivo by decreasing SIRT6 dependent glycolysis. Pharm. Biol. 2021, 59, 11–20. [Google Scholar] [CrossRef]
- Pan, Y.; Wang, W.; Huang, S.; Ni, W.; Wei, Z.; Cao, Y.; Yu, S.; Jia, Q.; Wu, Y.; Chai, C. Beta-elemene inhibits breast cancer metastasis through blocking pyruvate kinase M2 dimerization and nuclear translocation. J. Cell. Mol. Med. 2019, 23, 6846–6858. [Google Scholar] [CrossRef]
- Li, J.; Dai, P.; Sun, J.; Yu, W.; Han, W.; Li, K. FBP1 induced by β-elemene enhances the sensitivity of gefitinib in lung cancer. Thorac. Cancer 2023, 14, 371–380. [Google Scholar] [CrossRef]
- Park, M.K.; Ji, J.; Haam, K.; Han, T.-H.; Lim, S.; Kang, M.-J.; Lim, S.S.; Ban, H.S. Licochalcone A inhibits hypoxia-inducible factor-1α accumulation by suppressing mitochondrial respiration in hypoxic cancer cells. Biomed. Pharmacother. 2021, 133, 111082. [Google Scholar] [CrossRef]
- Han, S.; Li, X.; Gan, Y.; Li, W. Licochalcone A promotes the ubiquitination of c-met to abrogate gefitinib resistance. BioMed Res. Int. 2022, 2022, 5687832. [Google Scholar] [CrossRef]
- Yoon, Y.; Kim, Y.-O.; Jeon, W.-K.; Park, H.-J.; Sung, H.J. Tanshinone IIA isolated from Salvia miltiorrhiza BUNGE induced apoptosis in HL60 human premyelocytic leukemia cell line. J. Ethnopharmacol. 1999, 68, 121–127. [Google Scholar] [CrossRef] [PubMed]
- Li, M.; Gao, F.; Zhao, Q.; Zuo, H.; Liu, W.; Li, W. Tanshinone IIA inhibits oral squamous cell carcinoma via reducing Akt-c-Myc signaling-mediated aerobic glycolysis. Cell Death Dis. 2020, 11, 381. [Google Scholar] [CrossRef] [PubMed]
- Kim, D.H.; Sung, B.; Kang, Y.J.; Hwang, S.Y.; Kim, M.J.; Yoon, J.H.; Im, E.; Kim, N.D. Sulforaphane inhibits hypoxia-induced HIF-1α and VEGF expression and migration of human colon cancer cells. Int. J. Oncol. 2015, 47, 2226–2232. [Google Scholar] [CrossRef] [PubMed]
- Huang, L.; He, C.; Zheng, S.; Wu, C.; Ren, M.; Shan, Y. AKT1/HK2 Axis-mediated Glucose Metabolism: A Novel Therapeutic Target of Sulforaphane in Bladder Cancer. Mol. Nutr. Food Res. 2022, 66, e2100738. [Google Scholar] [CrossRef] [PubMed]
- Chen, C.-Y.; Yu, Z.-Y.; Chuang, Y.-S.; Huang, R.-M.; Wang, T.-C.V. Sulforaphane attenuates EGFR signaling in NSCLC cells. J. Biomed. Sci. 2015, 22, 38. [Google Scholar] [CrossRef] [PubMed]
- Gao, F.; Li, M.; Liu, W.-B.; Zhou, Z.-S.; Zhang, R.; Li, J.-L.; Zhou, K.-C. Epigallocatechin gallate inhibits human tongue carcinoma cells via HK2-mediated glycolysis. Oncol. Rep. 2015, 33, 1533–1539. [Google Scholar] [CrossRef] [PubMed]
- Yang, C.S.; Wang, X.; Lu, G.; Picinich, S.C. Cancer prevention by tea: Animal studies, molecular mechanisms and human relevance. Nat. Rev. Cancer 2009, 9, 429–439. [Google Scholar] [CrossRef]
- Liang, Y.C.; Lin-shiau, S.Y.; Chen, C.F.; Lin, J.K. Suppression of extracellular signals and cell proliferation through EGF receptor binding by (−)-epigallocatechin gallate in human A431 epidermoid carcinoma cells. J. Cell Biochem. 1997, 67, 55–65. [Google Scholar] [CrossRef]
- Adachi, S.; Nagao, T.; To, S.; Joe, A.K.; Shimizu, M.; Matsushima-Nishiwaki, R.; Kozawa, O.; Moriwaki, H.; Maxfield, F.R.; Weinstein, I.B. (−)-Epigallocatechin gallate causes internalization of the epidermal growth factor receptor in human colon cancer cells. Carcinogenesis 2008, 29, 1986–1993. [Google Scholar] [CrossRef]
- Meng, J.; Chang, C.; Chen, Y.; Bi, F.; Ji, C.; Liu, W. EGCG overcomes gefitinib resistance by inhibiting autophagy and augmenting cell death through targeting ERK phosphorylation in NSCLC. OncoTargets Ther. 2019, 12, 6033. [Google Scholar] [CrossRef]
- Chen, J.; Xie, J.; Jiang, Z.; Wang, B.; Wang, Y.; Hu, X. Shikonin and its analogs inhibit cancer cell glycolysis by targeting tumor pyruvate kinase-M2. Oncogene 2011, 30, 4297–4306. [Google Scholar] [CrossRef] [PubMed]
- Labrie, M.; Brugge, J.S.; Mills, G.B.; Zervantonakis, I.K. Therapy resistance: Opportunities created by adaptive responses to targeted therapies in cancer. Nat. Rev. Cancer 2022, 22, 323–339. [Google Scholar] [CrossRef] [PubMed]
- Ye, J.; Wu, J.; Liu, B. Therapeutic strategies of dual-target small molecules to overcome drug resistance in cancer therapy. Biochim. Biophys. Acta (BBA)-Rev. Cancer 2023, 1878, 188866. [Google Scholar] [CrossRef] [PubMed]
- Hsu, P.P.; Sabatini, D.M. Cancer cell metabolism: Warburg and beyond. Cell 2008, 134, 703–707. [Google Scholar] [CrossRef] [PubMed]
- Jin, L.; Cho, M.; Kim, B.-S.; Han, J.H.; Park, S.; Lee, I.-K.; Ryu, D.; Kim, J.H.; Bae, S.-J.; Ha, K.-T. Drug evaluation based on phosphomimetic PDHA1 reveals the complexity of activity-related cell death in A549 non-small cell lung cancer cells. BMB Rep. 2021, 54, 563. [Google Scholar] [CrossRef] [PubMed]
- Cragg, G.M.; Newman, D.J. Natural products: A continuing source of novel drug leads. Biochim. Et Biophys. Acta (BBA)-Gen. Subj. 2013, 1830, 3670–3695. [Google Scholar] [CrossRef]
- Harvey, A.L. Natural products in drug discovery. Drug Discov. Today 2008, 13, 894–901. [Google Scholar] [CrossRef]
- Roy, S.; Kumaravel, S.; Sharma, A.; Duran, C.L.; Bayless, K.J.; Chakraborty, S. Hypoxic tumor microenvironment: Implications for cancer therapy. Exp. Biol. Med. 2020, 245, 1073–1086. [Google Scholar] [CrossRef]
- Atanasov, A.G.; Zotchev, S.B.; Dirsch, V.M.; Supuran, C.T. Natural products in drug discovery: Advances and opportunities. Nat. Rev. Drug Discov. 2021, 20, 200–216. [Google Scholar] [CrossRef]
- Demain, A.L.; Vaishnav, P. Natural products for cancer chemotherapy. Microb. Biotechnol. 2011, 4, 687–699. [Google Scholar] [CrossRef]
- Tan, G.; Gyllenhaal, C.; Soejarto, D.D. Biodiversity as a source of anticancer drugs. Curr. Drug Targets 2006, 7, 265–277. [Google Scholar] [CrossRef]
- Rahmani, A.H.; Babiker, A.Y.; Anwar, S. Hesperidin, a Bioflavonoid in Cancer Therapy: A Review for a Mechanism of Action through the Modulation of Cell Signaling Pathways. Molecules 2023, 28, 5152. [Google Scholar] [CrossRef] [PubMed]
- Yenigun, O.M.; Thanassi, M. Capsaicin: An Uncommon Exposure and Unusual Treatment. Clin. Pract. Cases Emerg. Med. 2019, 3, 219–221. [Google Scholar] [CrossRef]
- Mereles, D.; Hunstein, W. Epigallocatechin-3-gallate (EGCG) for clinical trials: More pitfalls than promises? Int. J. Mol. Sci. 2011, 12, 5592–5603. [Google Scholar] [CrossRef] [PubMed]
- Salehi, B.; Venditti, A.; Sharifi-Rad, M.; Kręgiel, D.; Sharifi-Rad, J.; Durazzo, A.; Lucarini, M.; Santini, A.; Souto, E.B.; Novellino, E.; et al. The Therapeutic Potential of Apigenin. Int. J. Mol. Sci. 2019, 20, 1305. [Google Scholar] [CrossRef]
- Lozanovski, V.J.; Polychronidis, G.; Gross, W.; Gharabaghi, N.; Mehrabi, A.; Hackert, T.; Schemmer, P.; Herr, I. Broccoli sprout supplementation in patients with advanced pancreatic cancer is difficult despite positive effects-results from the POUDER pilot study. Investig. New Drugs 2020, 38, 776–784. [Google Scholar] [CrossRef] [PubMed]
- Wu, Q.; Ouyang, Y.; Kong, Y.; Min, Y.; Xiao, J.; Li, S.; Zhou, M.; Feng, N.; Zhang, L. Catechin Inhibits the Release of Advanced Glycation End Products during Glycated Bovine Serum Albumin Digestion and Corresponding Mechanisms In Vitro. J. Agric. Food Chem. 2021, 69, 8807–8818. [Google Scholar] [CrossRef]
- Hewlings, S.J.; Kalman, D.S. Curcumin: A Review of Its Effects on Human Health. Foods 2017, 6, 92. [Google Scholar] [CrossRef]
- Xing, L.; Tan, Z.R.; Cheng, J.L.; Huang, W.H.; Zhang, W.; Deng, W.; Yuan, C.S.; Zhou, H.H. Bioavailability and pharmacokinetic comparison of tanshinones between two formulations of Salvia miltiorrhiza in healthy volunteers. Sci. Rep. 2017, 7, 4709. [Google Scholar] [CrossRef]
- Solnier, J.; Zhang, Y.; Kuo, Y.C.; Du, M.; Roh, K.; Gahler, R.; Wood, S.; Chang, C. Characterization and Pharmacokinetic Assessment of a New Berberine Formulation with Enhanced Absorption In Vitro and in Human Volunteers. Pharmaceutics 2023, 15, 2567. [Google Scholar] [CrossRef]
- Song, M.; Lee, D.; Lee, T.; Lee, S. Determination of leelamine in mouse plasma by LC-MS/MS and its pharmacokinetics. J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 2013, 931, 170–173. [Google Scholar] [CrossRef] [PubMed]
- Li, H.-L.; Qin, Z.-M.; Cai, H.-D.; Tan, Y.-F.; Zhang, X.-P.; Luo, Y.-C.; Li, B.; Chen, F.; Zhang, J.-Q. Determination of α-hederin in rat plasma using liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) and its application to a pharmacokinetic study. Anal. Methods 2015, 7, 2155–2161. [Google Scholar] [CrossRef]
- Hao, H.; Wang, G.; Cui, N.; Li, J.; Xie, L.; Ding, Z. Pharmacokinetics, absorption and tissue distribution of tanshinone IIA solid dispersion. Planta Med. 2006, 72, 1311–1317. [Google Scholar] [CrossRef] [PubMed]
- Sun, C.; Zhao, W.; Wang, X.; Sun, Y.; Chen, X. A pharmacological review of dicoumarol: An old natural anticoagulant agent. Pharmacol. Res. 2020, 160, 105193. [Google Scholar] [CrossRef] [PubMed]
- Jinhua, W. Ursolic acid: Pharmacokinetics process in vitro and in vivo, a mini review. Arch. Pharm. 2019, 352, e1800222. [Google Scholar] [CrossRef] [PubMed]
- Yang, Z.; Kulkarni, K.; Zhu, W.; Hu, M. Bioavailability and pharmacokinetics of genistein: Mechanistic studies on its ADME. Anticancer. Agents Med. Chem. 2012, 12, 1264–1280. [Google Scholar] [CrossRef] [PubMed]
- Sun, Q.; Gong, T.; Liu, M.; Ren, S.; Yang, H.; Zeng, S.; Zhao, H.; Chen, L.; Ming, T.; Meng, X.; et al. Shikonin, a naphthalene ingredient: Therapeutic actions, pharmacokinetics, toxicology, clinical trials and pharmaceutical researches. Phytomedicine 2022, 94, 153805. [Google Scholar] [CrossRef] [PubMed]
- Zhai, B.; Zeng, Y.; Zeng, Z.; Zhang, N.; Li, C.; Zeng, Y.; You, Y.; Wang, S.; Chen, X.; Sui, X.; et al. Drug delivery systems for elemene, its main active ingredient β-elemene, and its derivatives in cancer therapy. Int. J. Nanomed. 2018, 13, 6279–6296. [Google Scholar] [CrossRef]
- Li, T.; Ye, W.; Huang, B.; Lu, X.; Chen, X.; Lin, Y.; Wen, C.; Wang, X. Determination and pharmacokinetic study of echinatin by UPLC-MS/MS in rat plasma. J. Pharm. Biomed. Anal. 2019, 168, 133–137. [Google Scholar] [CrossRef]
- Liu, J.; Zhu, Z.; Yang, Y.; Adu-Frimpong, M.; Chen, L.; Ji, H.; Toreniyazov, E.; Wang, Q.; Yu, J.; Xu, X. Preparation, characterization, pharmacokinetics, and antirenal injury activity studies of Licochalcone A-loaded liposomes. J. Food Biochem. 2022, 46, e14007. [Google Scholar] [CrossRef]
Drug | Structure | Drug Type | FDA Approval |
---|---|---|---|
Erlotinib (TarcevaTM) | 1st-generation EGFR-TKI | 1st-line, NSCLC with EGFR19D/EGFRL858R [74] | |
Gefitinib (IressaTM) | 1st-generation EGFR-TKI | 1st-line, NSCLC with EGFR19D/EGFRL858R [28] | |
Afatinib (GilotrifTM) | 2nd-generation EGFR-TKI | 1st-line, NSCLC with EGFR19D/EGFRL858R [25] | |
Dacomitinib (VizimproTM) | 2nd-generation EGFR-TKI | 1st-line, NSCLC with EGFR19D/EGFRL858R [26] | |
Mobocertinib (ExkivityTM) | 3rd-generation EGFR-TKI | NSCLC with EGFR exon20 insertion [75] | |
Osimertinib (TagrissoTM) | 3rd-generation EGFR-TKI | 2nd-line, NSCLC with EGFRT790M [76] 1st-line, NSCLC with EGFR19D/EGFRL858R [77] adjuvant therapy for NSCLC [78] |
PDK Inhibitor | Structure | Property | Origin | Clinical Trials for NSCLC | Reference |
---|---|---|---|---|---|
Cryptotanshinone | IC50: PDK2 (11 µM), PDK4 (>30 µM) | Salvia miltiorrhiza | ND | [113] | |
Dicoumarol | IC50: PDK1 (19.42 μM) | Melilotus officinalis | ND | [112] | |
Hemistepsin A | ND | Hemistepta lyrate | ND | [18] | |
Huzhangoside A | ND | Anemone rivularis | ND | [19] | |
Ilimaquinone | ND | Smenospongia cerebriformis | ND | [20] | |
Leelamine | IC50: 9.5 µM | bark of pine trees | ND | [120] | |
Otobaphenol | ND | Myristica fragrans | ND | [121] | |
Quercetin | IC50: PDK3 (~9.5 μM), | flavonoid glycosides from fruits and vegetables | ND | [122] |
LDHA Inhibitor | Structure | Property | Origin | Clinical Trials for NSCLC | Reference |
---|---|---|---|---|---|
Apigenin | IC50: LDHA (0.042 mM) | Flavonoid from fruits, vegetables, and herbs | ND | [139] | |
Berberine | ND | Goldenseal (Hydrastis canadensis) | NCT03486496 | [140] | |
Capsaicin | ND | Capsicum annuum | ND | [141] | |
Catechin | IC50: LDHA (40.69 μM) | Camellia sinensis | NCT00573885 NCT00611650 | [14] | |
Curcumin | ND | Curcuma longa | NCT02321293 NCT01048983 | [143] | |
Epigallocatechin gallate | ND | Camellia sinensis | ND | [146] | |
Galloflavin | IC50: LDHA (5.46 μM) | Flavonoid from food and vegetables | ND | [150] | |
Leonurine | ND | Leonurus cardiaca | ND | [151] | |
Quercetin | ND | Quercus, Flavonoid glycosides from fruits and vegetables | ND | [152] | |
Ursolic acid | ND | Triterpenoid from citrus fruits and vegetables | ND | [154] |
Glycolysis Inhibitor | Structure | Effect | Origin | Clinical Trials for NSCLC | Reference |
---|---|---|---|---|---|
α-Hederin | GLUT1, PKM2, LDHA, and HK2↓ | Hedera helix | ND | [159] | |
β-elemene | PKM2↓ | Curcuma aromatica | ND | [160] | |
Cucurbitacin D | Glut1↓ | Cucurbitaceae | ND | [155] | |
Epigallocatechin gallate | HK2↓ | Green tea | ND | [169] | |
Genistein | HIF-1α, GLUT1, and HK2↓ | Lupin, fava beans, soybeans, kudzu, and psoralea | NCT01628471 NCT00769990 | [157] | |
Licochalcone A | HIF-1α, PDK1, and GLUT1↓ | Glycyrrhiza uralensis | ND | [162] | |
Shikonin | PKM2↓ | lithospermum erythrorhizon | ND | [174] | |
Sulforaphane | HIF-1α, HK2, and PKM2↓ | Broccoli | ND | [166,167] | |
Tanshinone IIA | HK2↓ | Salvia miltiorrhiza | ND | [165] |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Park, W.; Han, J.H.; Wei, S.; Yang, E.-S.; Cheon, S.-Y.; Bae, S.-J.; Ryu, D.; Chung, H.-S.; Ha, K.-T. Natural Product-Based Glycolysis Inhibitors as a Therapeutic Strategy for Epidermal Growth Factor Receptor–Tyrosine Kinase Inhibitor-Resistant Non-Small Cell Lung Cancer. Int. J. Mol. Sci. 2024, 25, 807. https://doi.org/10.3390/ijms25020807
Park W, Han JH, Wei S, Yang E-S, Cheon S-Y, Bae S-J, Ryu D, Chung H-S, Ha K-T. Natural Product-Based Glycolysis Inhibitors as a Therapeutic Strategy for Epidermal Growth Factor Receptor–Tyrosine Kinase Inhibitor-Resistant Non-Small Cell Lung Cancer. International Journal of Molecular Sciences. 2024; 25(2):807. https://doi.org/10.3390/ijms25020807
Chicago/Turabian StylePark, Wonyoung, Jung Ho Han, Shibo Wei, Eun-Sun Yang, Se-Yun Cheon, Sung-Jin Bae, Dongryeol Ryu, Hwan-Suck Chung, and Ki-Tae Ha. 2024. "Natural Product-Based Glycolysis Inhibitors as a Therapeutic Strategy for Epidermal Growth Factor Receptor–Tyrosine Kinase Inhibitor-Resistant Non-Small Cell Lung Cancer" International Journal of Molecular Sciences 25, no. 2: 807. https://doi.org/10.3390/ijms25020807