Oncology

History, development directions

and prospects of oncology
Lecture: History, development directions and prospects of oncology
By Professor: Armine Andryan
Ministry of Health<Disease control and prevention
National Center> SNCO "Shirak" Branch Deputy Director,
Coordinator of Epidemiology
 Oncology
 Greek: oncos-tumor, logos-speech, science. Oncology is a branch of
medicine that studies the causes, mechanisms of development and
clinical manifestations of tumors.
History of oncology - Back in ancient Egypt (2nd millennium BC),
doctors surgically removed breast tumors. In ancient Greece in the 4th
century, Hippocrates used the term carcinos to describe tumors. The
famous Roman doctor Galen in the 2nd century used the word cancer,
likening the malignant tumor of the mammary gland to cancer. He is
also credited with the use of the Greek word ὄγκος - swelling, from
which the term Oncologia (English Oncology) later arose.
In 1946 The Institute of Roentgenology, Radiology and Oncology (now
the National Oncology Center) was founded in Yerevan. In the 1970s, a
course in oncology was opened at YSMU, then a chair under M. Kh.
Hayrapetyan’s leadership.
 Development directions and
perspectives
Diagnosis
 New diagnosis of malignant tumors, follow-up of patients
development of algorithms
 Improvement and application of the researches of RN, MS,
MRS, PES and other researches differential diagnosis and
determination of the stage of the disease, the result of
treatment for assessment
 Improvement of methods of interventional radiology
 Development and application of immuno-morphological,
immuno-histochemical, molecular biological examination
methods of tumors in the clinic
 Treatment
 Development of new algorithms for combined and complex
treatment
 Endoscopic, organ-preserving, extensive, ultra-extensive,
combined investigation of indications, adequacy of surgical
interventions, justification
 New chemical preparations, hormonal, biological preparations,
discovery and testing of protectors
 In order to improve the quality of patients’ life receiving
antitumor treatment development of targeted measures
 Development of new approaches to radiation treatment,
existing methods improvement: latest technologies,
radiobiology, molecular based on achievements in oncology.
 Basic research

 The assessment of Genetic predisposition to tumor diseases

 Investigating tumor growth regulation mechanisms
 The course of the tumor process, the sensitivity to treatment,
the disease development of new laboratory methods for yield
assessment
 Development of new approaches to tumor biotherapy
 Targeting the selectivity of cytostatic effects research etc.
 Tumor and carcinogenesis
 Cell proliferation (cell multiplication and growth) is controlled genetically by
the cell by the hardware. Each cell inherits genes from its ancestor and
passes on to its descendants. This process is normally under the highly
balanced control of the genetic apparatus.
 In the process of developing a malignant tumor, such genetic control is
disrupted or lost in one or more cells, they lose the ability to respond to
genetic signals that inhibit cell proliferation and growth, causing the cells to
divide endlessly.
 Accumulations of such abnormal cells (tumors) cause damage to adjacent
tissues. Cells from their "place of birth" can spread through the
bloodstream and lymph, forming colonies (metastases), eventually leading
to the death of the organism.
A tumor is a pathological tissue whose development is based on disorders of
growth, reproduction and differentiation caused by changes in the genetic
apparatus of cells.
 Benign and malignant tumors
Benign and malignant tumors are distinguished, the biological
characteristics of which are presented in table 1:
Benign tumors Malignant tumors
 Have a pod (capsule)  Absence of capsule
 Expansive growth  Infiltrative growth
Highly differentiated  Have low differentiation, cause
structure atypical structures
 Cellular and tissue atypisms
Tissue atypism
 Large number of mitoses
Few mitoses  Rapid growth
 Slow growth  They metastasize
They do not metastasize  They show not only local effect on
 Local effect on the body the organism, but also general
impact
Benign tumors

 Benign tumor cells are the same or similar in structure

corresponding to the cells of normal tissue, preserve the
functional features characteristic of the tissue. They grow
slowly, do not cause metastases and are considered benign
from a clinical and prognostic point of view.
Malignant tumors

 Malignant tumor cells are structurally different (often

unrecognizably) from the cells which correspond to
normal tissue, give rise to structures not
characteristic of the tissue. They grow faster, grow
into neighboring tissues, spread through blood and
lymph flow causing metastases.
 Destructive tumors
 Demarcation of benign and malignant tumors is done mainly
on the basis of morphological signs and above all for practical
reasons.
 Tumors with local destructive growth are also distinguished,
which seem to take an intermediate position between benign
and malignant tumors - they have infiltrative growth, but do
not metastasize - basal cell carcinoma, desmoid fibroma, some
post-abdominal tumors, myxoma, juvenile angioma, etc.
 Carcinogenesis
 During normal development of an organism, complex regulatory mechanisms
ensure the required type and quantity of cells in each tissue occurrence. Under the
influence of various factors, a frequent occurrence in the genetic apparatus of the
cell have structural changes - mutations.
 Mutations depending on their location, in one way or another can affect cell
viability and on functional status. Malignant transformation has been found to be
associated with such genes with mutations that are responsible for cell growth,
reproduction. Carcinogenesis leads to sequential mutations in "fatal" genes.
 As a result of mutation, the cell acquires a biological advantage over other
surrounding cells - cloning.
 A population of cells with characteristics of malignancy emerges with all features.
• with cell immortality
• with relative autonomy
• with atypism
• with invasive growth
• with metastasis.
 Carcinogenesis
So
a. malignant tumors are of clonogenic origin,
b. tumorigenesis is a multistage and "multigenic" process.
Proto-oncogenes are a component of the normal cell genome, responsible
for promoting cell proliferation․
Oncoproteins are usually endowed with enzymatic activity and are one of
the main factors in the intracellular transmission of proliferative signals.
In the process of transformation, under the influence of certain factors, the
proto-oncogene turns into an oncogene․
The mechanisms of activation of proto-oncogenes are different․
 Point mutation of proto-oncogene,
 Suppressor gene point mutations
 Proto-oncogene amplification
 Insertional activation
 Deletion, translocation, chromosomal aberrations
Օncogenes and suppressor genes
For example
 Օncogenes -the oncogene aml1 encodes a transcription factor
and causes acute myeloid leukemia, or the oncogene L-myc
activates a transcription factor and causes lung cancer.
 Suppressor genes- BRCA1, BRCA2 oncogene ensures repair of
DNA damage and causes hereditary breast cancer, ovarian
cancer, or VHL oncogene as cell cycle regulator; May increase
p53-activity and stability, causing Renal cell carcinoma.

The longer an organism lives, the greater the regulation of cell

division the possibility of gene damage under the influence of
external and internal damaging factors.
Stem cells, cell immortality and
telomeres
Normal somatic cells have reproductive cycles (successive cell divisions)
number limit called the Heitflick partition limit. This limitation
mechanism is based on the ends of chromosomes, telomeres.
Unlike somatic cells, stem cells In 80-90% of cells and tumors, the
activity of the telomerase enzyme is high, due to which telomeres are
constantly renewed, which determines the ability of the cell to
endlessly reproduce itself and "immortality".
In recent years, stemness in tumorigenesis has been widely discussed
the role of cells. For tumorigenesis (tumorigenesis), the cell must also
possess the so-called self-regeneration/self-reproduction property. As a
result of mutations in the process of oncogenesis, the stem cell turns
into a tumor stem cell.
 Apoptosis
We have often discussed the uncontrolled growth of malignant
tumors from the point of view of proliferation, but there is also
another factor, that is cell death. Cells need <growth stimuli> to
maintain homeostasis and viability. Deprived of these signals,
cells undergo apoptosis (programmed death, suicide).
It has been shown to be highly oncogenic mutations (for
example, activation of the Mic proto-oncogene, inactivation of
the Rb suppressor gene) are triggers (initiators) and promoters
of apoptosis (promoters).
 Stages of carcinogenesis
As mentioned above, tumorigenesis (carcinogenesis) or tumor
transformation is a multistep process. Conventionally they
differentiate the following stages of carcinogenesis.
 Initiation- occurs due to various origins (physical, influence of
chemical, biological) carcinogenic factors
 Promotion- are mitogenic factors that stimulate cell proliferation
 Progression- For cells to become tumorigenic, they must also avoid
further differentiation. Occurs genetic new mutations appearing on
the background of instability, in the gene coding micro-RNAs,
resulting in tumorigenic clones.
Thus, tumor progression is characterized by both quantitative and
qualitative serious changes in the tumor tissue, during which the
degree of atypia and anaplasia of tumor cells increases.
 Kinetics of tumor growth
From the initiation of tumor growth to
the appearance of a clinically detectable
(diagnosable) tumor, it can take from
several years to several decades, that is,
until the development of the clinical
picture of malignant tumor disease is
preceded by a rather long "latent period
", when a tumor clone is formed as a
result of successive mutations.
Even with the diagnosis of "early
cancer", the "history" of the
development of the tumor process the
majority is already behind.
Kinetics of tumor growth

Rapidly growing tumors are most characterized by a short

cell cycle. Not all cells in tumor tissue are proliferating
(dormant cells). Tumors in the majority, actively dividing
cells or the so-called proliferative part (pool) makes up only
5-30% of tumor cells. Obviously, how big the proliferative
phase, the faster the tumor grows.
Some of the cells are destroyed during the tumor process:
non-viable daughter cells, apoptosis, necrosis, metastasis,
etc.