ONCOLOGY

INTRODUCTION:
Cancer is a class of diseases characterized by out-of-control cell growth. There are over 100 different types of cancer, and each is classified by the type of cell that is initially affected. Cancer harms the body when damaged cells divide uncontrollably to form lumps or masses of tissue called tumors (except in the case of leukemia where cancer prohibits normal blood function by abnormal cell division in the blood stream). Tumors can grow and interfere with the digestive, nervous, and circulatory systems and they can release hormones that alter body function. Tumors that stay in one spot and demonstrate limited growth are generally considered to be benign.

HISTORY:
The world's first documented case of cancer hails from ancient Egypt, in 1500 b.c. The details were recorded on a papyrus, documenting 8 cases of tumors occurring on the breast. It was treated by cauterization, a method to destroy tissue with a hot instrument called "the fire drill." It was also recorded that there was no treatment for the disease, only palliative treatment. There is evidence that the ancient Egyptians were able to tell the difference between malignant and benign tumors. According to inscriptions, surface tumors were surgically removed in a similar manner as they are removed today.

ORIGIN OF THE WORD CANCER:

The origin of the word cancer is credited to the Greek physician Hippocrates (460-370 BC), who is considered the Father of Medicine. Hippocrates used the terms carcinosand carcinoma to describe non-ulcer forming and ulcer-forming tumors. In Greek, these words refer to a crab, most likely applied to the disease because the finger-like spreading projections from a cancer called to mind the shape of a crab. The Roman physician, Celsus

(28-50 BC), later translated the Greek term into cancer, the Latin word for crab. Galen (130-200 AD), another Roman physician, used the word oncos (Greek for swelling) to describe tumors. Although the crab analogy of Hippocrates and Celsus is still used to describe malignant tumors, Galens term is now used as a part of the name for cancer specialists oncologists. During the Renaissance, beginning in the 15th century, scientists developed greater understanding of the human body. Scientists like Galileo and Newton began to use the scientific method, which later was used to study disease. Autopsies, done by Harvey (1628), led to an understanding of the circulation of blood through the heart and body that had until then been a mystery. In 1761, Giovanni Morgagni of Padua was the first to do something which has become routine today he did autopsies to relate the patients illness to pathologic findings after death. This laid the foundation for scientific oncology, the study of cancer. The famous Scottish surgeon John Hunter (17281793) suggested that some cancers might be cured by surgery and described how the surgeon might decide which cancers to operate on. If the tumor had not invaded nearby tissue and was moveable, he said, There is no impropriety in removing it. A century later the development of anesthesia allowed surgery to flourish and classic cancer operations such as the radical mastectomy were developed. The 19th century saw the birth of scientific oncology with use of the modern microscope in studying diseased tissues. Rudolf Virchow, often called the founder of cellular pathology, provided the scientific basis for the modern pathologic study of cancer. As Morgagni had linked autopsy findings seen with the unaided eye with the clinical course of illness, so Virchow correlated microscopic pathology to illness. This method not only allowed a better understanding of the damage cancer had done, but also aided the development of cancer surgery. Body tissues removed by the surgeon could now be examined and a precise diagnosis could be made. The pathologist could also tell the surgeon whether the operation had completely removed the cancer.

CANCER CAUSES: THEORIES THROUGHOUT HISTORY From the earliest times, physicians have puzzled over the causes of cancer. Ancient Egyptians blamed cancers on the gods. There are certain theories related to the causes of cancer.

HUMORAL THEORY Hippocrates believed that the body had 4 humors (body fluids) :blood, phlegm, yellow bile, and black bile. When the humors were balanced, a person was healthy. Too much or too little of any of the humors caused disease. An excess of black bile in various body sites was thought to cause cancer. This theory of cancer was passed on by the Romans and was embraced by the influential doctor Galens medical teaching, which remained the unchallenged standard through the Middle Ages for over 1,300 years. During this period, the study of the body, including autopsies, was prohibited for religious reasons, which limited progress of medical knowledge. LYMPH THEORY Among theories that replaced the humoral theory of cancer, was the formation of cancer by another body fluid, lymph. Life was believed to consist of continuous and appropriate movement of the fluid parts of the body through the solid parts. Of all the fluids, the most important were blood and lymph. Stahl and Hoffman theorized that cancer was composed of fermenting and degenerating lymph varying in density, acidity, and alkalinity. The lymph theory gained rapid support. The eminent Scottish surgeon John Hunter (17281793) agreed that tumors grow from lymph constantly thrown out by the blood.

BLASTEMA THEORY In 1838, German pathologist Johannes Muller demonstrated that cancer is made up of cells and not lymph, but he believed that cancer cells did not come from normal cells. Muller proposed that cancer cells developed from budding elements (blastema) between normal tissues. His student, Rudolph Virchow (18211902), the famous German pathologist, determined that all cells, including cancer cells, are derived from other cells.

CHRONIC IRRITATION THEORY Virchow proposed that chronic irritation was the cause of cancer, but he falsely believed that cancers spread like a liquid. In the 1860s, German surgeon, Karl Thiersch, showed that cancers metastasize through the spread of malignant cells and not through some unidentified fluid. TRAUMA THEORY
Despite advances in the understanding of cancer, from the late 1800s until the 1920s, trauma was thought by some to cause cancer. This belief was maintained despite the failure of injury to cause cancer in experimental animals.

PARASITIC THEORY
Zacutus Lusitani (15751642) and Nicholas Tulp (15931674), 2 doctors in Holland, concluded at almost the same time that cancer was contagious. They made this conclusion based on their experiences with breast cancer in members of the same household. Lusitani and Tulp publicized the contagion theory in 1649 and 1652, respectively. They proposed that cancer patients should be isolated, preferably outside of cities and towns, in order to prevent the spread of cancer. Throughout the 17th and 18th centuries, some believed that cancer was contagious. In fact, the first cancer hospital in France was forced to move from the city in 1779 because people feared cancer would spread throughout the city. Although human cancer, itself, is not contagious, we now know that certain viruses, bacteria, and parasites can increase a persons risk of developing cancer.

CAUSES:
Researchers divide the causes of cancer into two groups: those with an environmental cause and those with a hereditary genetic cause. Cancer is primarily an environmental disease, though genetics influence the risk of some cancers. Common environmental factors leading to cancer include: tobacco, diet and obesity, infections, radiation, lack of physical activity, and environmental pollutants. These environmental factors cause or enhance abnormalities in the genetic material of cells. Cell reproduction is an extremely complex process that is normally tightly regulated by several classes of genes, including oncogenes and tumor suppressor genes. Hereditary or acquired abnormalities in these regulatory genes can lead to the development of cancer. A small percentage of cancers, approximately five to ten percent, are entirely hereditary.

TUMOR:
Tumor is mass of cells which have escaped normal growth and development. It is also called neoplasm which literally means new but abnormal growth. Normal cell give rise to neoplasm and this may happen in any tissue of the body. More than 100 neoplasm have been discovered so far but only two of them are having distinguishing features.

BENIGN TUMOR:
It is abnormal growth confined to its location. Its characteristic is that neither it invades the surrounding tissue nor it spreads to distal organs. It can be removed through surgeries and is rarely fatal.

MALIGNANT TUMOR:
It is the real cancer which is both invasive and metastatic i:e it has the capability of invading the neighboring tissues as well as spreading to distal organs via circulatory system.

TYPES OF TUMOR ON THE BASIS OF ORIGIN:

Cancers are classified by the type of cell that the tumor resembles and is therefore presumed to be the origin of the tumor. These types include:

Carcinoma: Cancer derived from epithelial cells. This group includes many of the most common cancers, including those of the breast, prostate, lung and colon. Sarcoma: Sarcomas are characterized by cells that are located in bone, cartilage, fat, connective tissue, muscle, and other supportive tissues. Lymphoma and leukemia: Cancer derived from hematopoietic (bloodforming) cells Adenomas are cancers that arise in the thyroid, the pituitary gland, the adrenal gland, and other glandular tissues. Germ cell tumor: Cancer derived from pluripotent cells. In adults these are most often found in the testicle and ovary, but are more common in babies and young children. Blastoma: Cancer derived from immature "precursor" or embryonic tissue. These are also commonest in children.

STAGES OF CANCER:
By determining the correct stage of cancer a physician can plan the best therapy and evaluate the results. The earlier the stage, the greater are opportunities to cure the disease. Stages of cancer are: Stage I: Simplest form, indicating that cancer is confined to local tissue. Greater chance of cure. Stage II: The tumor spreads to neighboring tissues. Chances of cure are 50%. Stage III: The tumor spreads to lymph nodes. Cure becomes very harder. Stage IV: It signifies the most extensive spread of cancer. Chances of cure are negligible.

SYMPTOMS:

Local symptoms: are restricted to the site of the primary cancer. They can include lumps or swelling (tumor), hemorrhage (bleeding from the skin, mouth or anus), ulceration and pain. Although local pain commonly occurs in advanced cancer. Metastatic symptoms: are due to the spread of cancer to other locations in the body. They can include enlarged lymph nodes (which can be felt or sometimes seen under the skin), hepatomegaly (enlarged liver) or splenomegaly (enlarged spleen) which can be felt in the abdomen, pain or fracture of affected bones, and neurological symptoms. Systemic symptoms: occur due to distant effects of the cancer that are not related to direct or metastatic spread. Some of these effects can include weight loss (poor appetite and cachexia), fatigue, excessive sweating (especially night sweats), anemia (low red blood cell count) and other specific conditions termed paraneoplastic phenomena. These may be mediated by immunological or hormonal signals from the cancer cells. None of these are diagnostic, as many of these symptoms commonly occur in patients who do not have cancer.

DIAGNOSIS:
Most cancers are initially recognized either because signs or symptoms appear or through screening. Neither of these leads to a definitive diagnosis, which usually requires the opinion of a pathologist, a type of physician (medical doctor) who specializes in the diagnosis of cancer and other diseases. People with suspected cancer are investigated with medical tests. These commonly include blood tests, X-rays, CT scans and endoscopy.

PREVENTION:
Cancer prevention is defined as active measures to decrease the incidence of cancer. The vast majority of cancer risk factors are environmental or lifestyle-related, thus cancer is largely a preventable disease. Greater than 30% of cancer is preventable via avoiding risk factors including: tobacco, overweight or obesity, low fruit and vegetable intake, physical inactivity, alcohol, sexually transmitted infections, and air pollution.

RESEARCH:
Cancer research is the intense scientific effort to understand disease processes and discover possible therapies. For this purpose scientists used animal models in which cancer was induced by Radiations, Carcinogenic chemicals or oncogenic viruses. The most preferable one is the usage of oncogenic viruses because of their small genome and short onset of disease. Research about cancer causes focuses on the following issues:

Agents (e.g. viruses) and events (e.g. mutations) which cause or facilitate genetic changes in cells destined to become cancer. The precise nature of the genetic damage, and the genes which are affected by it. The consequences of those genetic changes on the biology of the cell, both in generating the defining properties of a cancer cell, and in facilitating additional genetic events which lead to further progression of the cancer.

DIFFERENCE BETWEEN NORMAL CELLS AND CANCEROUS CELLS:

Normal Cells 1. Structure DNA in genes and chromosomes go about their business in a normal way. Cells divide in an orderly way to produce more cells only when the body needs them. Cancer cells develop different mutations or acquire abnormal numbers of chromosomes. Cells continue to be created without control or order. If not needed, a mass of tissue is formed, which is called a tumor Cells have a defective "Krebs Cycle" and derive little or no Cancer Cells

2. Energy Cells derive 70% of their energy from a system called the "Krebs

Cycle. Cells derive only 20% of their energy from a system called "Glycolysis." Cells derive most of their energy with the use of oxygen.

energy from it Cancer cells derive almost all their energy from "Glycolysis." Cells derive most of their energy in the absence of oxygen. Cells dont have a built-in blood vessel system. They require more of certain amino acids to build one.

3. Blood Vessels Cells have a built-in blood vessel system.

4. Growth Factors While similar to cancer cells, the amount of them is more in balance to produce a more normal level of activity. The enzymes and hormones go about business in a normal balanced manner. These cells have over produced, require more chemicals (food) and are over active

5. Functions The enzymes and hormones are either over active or under active.

6. Life Span Normal cells are mortal. They Cancerian cells are immortal. divide up to a certain stage of life. They divide abnormally without E.g. some cells can grow only up stopping their division. to 50 cycles. 7. Morphology They are flat. They are round in shape.

8. Contact Inhibition They divide at the surface and form monolayer upon finding neighboring cells. They even upon finding neighboring cells proliferate and form a pillar of cells.

9. Anchorage dependency They require certain support and They can divide in the absence of anchor for growth. anchorage. 10. They do not produce toxicity. Toxicity They produce toxic material.

HOW IS CANCER TREATED?

Cancer treatment depends on the type of cancer, the stage of the cancer (how much it has spread), age, health status, and additional personal characteristics. There is no single treatment for cancer, and patients often receive a combination of therapies and palliative care. Treatments usually fall into one of the following categories: surgery, radiation, chemotherapy, immunotherapy, hormone therapy, or gene therapy.

SURGERY
Surgery is the oldest known treatment for cancer. If a cancer has not metastasized, it is possible to completely cure a patient by surgically removing the cancer from the body. This is often seen in the removal of the prostate or a breast or testicle. After the disease has spread, however, it is nearly impossible to remove all of the cancer cells. Surgery may also be instrumental in helping to control symptoms such as bowel obstruction or spinal cord compression.

RADIATION
Radiation treatment, also known as radiotherapy, destroys cancer by focusing high-energy rays on the cancer cells. This causes damage to the molecules that make up the cancer cells and leads them to commit suicide. Radiotherapy utilizes high-energy gamma-rays that are emitted from metals such as radium or high-energy x-rays that are created in a special machine. Early radiation treatments caused severe side-effects because the energy beams would damage normal, healthy tissue, but technologies have improved so that beams can be more accurately targeted. Radiotherapy is used as a standalone treatment to shrink a tumor or destroy cancer cells (including those associated with leukemia and lymphoma), and it is also used in combination with other cancer treatments.

CHEMOTHERAPY
Chemotherapy utilizes chemicals that interfere with the cell division process - damaging proteins or DNA - so that cancer cells will commit suicide. These treatments target any rapidly dividing cells (not necessarily just cancer cells), but normal cells usually can recover from any chemical-induced damage while cancer cells cannot. Chemotherapy is generally used to treat cancer that has spread or metastasized because the medicines travel throughout the entire body. It is a necessary treatment for some forms of leukemia and lymphoma. Chemotherapy treatment occurs in cycles so the body has time to heal between doses. However, there are still common side effects such as hair loss, nausea, fatigue, and vomiting. Combination therapies often include multiple types of chemotherapy or chemotherapy combined with other treatment options.

Immunotherapy
Immunotherapy aims to get the body's immune system to fight the tumor. Local immunotherapy injects a treatment into an affected area, for example, to cause inflammation that causes a tumor to shrink. Systemic immunotherapy treats the whole body by administering an agent such as the protein interferon alpha that can shrink tumors. Immunotherapy can also be considered non-specific if it improves cancer-fighting abilities by stimulating the entire immune system, and it can be considered targeted if the treatment specifically tells the immune system to destroy cancer cells. These therapies

are relatively young, but researchers have had success with treatments that introduce antibodies to the body that inhibit the growth of breast cancer cells. Bone marrow transplantation (hematopoetic stem cell transplantation) can also be considered immunotherapy because the donor's immune cells will often attack the tumor or cancer cells that are present in the host.

HORMONE THERAPY
Several cancers have been linked to some types of hormones, most notably breast and prostate cancer. Hormone therapy is designed to alter hormone production in the body so that cancer cells stop growing or are killed completely. Breast cancer hormone therapies often focus on reducing estrogen levels (a common drug for this is tamoxifen) and prostate cancer hormone therapies often focus on reducing testosterone levels. In addition, some leukemia and lymphoma cases can be treated with the hormone cortisone.

GENE THERAPY:
The goal of gene therapy is to replace damaged genes with ones that work to address a root cause of cancer: damage to DNA. For example, researchers are trying to replace the damaged gene that signals cells to stop dividing (the p53 gene) with a copy of a working gene. Other gene-based therapies focus on further damaging cancer cell DNA to the point where the cell commits suicide. Gene therapy is a very young field and has not yet resulted in any successful treatments.

ANGIOGENESIS INHIBITORS:
Angiogenesis is the creation of new blood vessels. The term comes from 2 Greek words: angio, meaning blood vessel, and genesis, meaning beginning. Normally, this is a healthy process. New blood vessels, for instance, help the body heal wounds and repair damaged tissues. But in a person with cancer, this same process creates new, very small blood vessels that give a tumor its own blood supply and allow it to grow. Anti-angiogenesis is a form of targeted therapy that uses drugs or other substances to stop tumors from making the new blood vessels they need to continue growing. This concept was first proposed by Judah Folkman in the early 1970s, but it

wasnt until 2004 that the first angiogenesis inhibitor, bevacizumab (Avastin), was approved for clinical use. Currently used to treat advanced colorectal, kidney, and lung cancers, bevacizumab is being studied as treatment for many other types of cancer, too. And many new drugs that block angiogenesis have become available since this first one in 2004. Apoptosis-inducing drugs Apoptosis is a natural process through which cells with DNA too damaged to repair such as cancer cells can be forced to die. Many anticancer treatments (including radiation and chemo) cause cell changes that eventually lead to apoptosis. But targeted drugs in this group are different, because they are aimed specifically at the cell substances that control cell survival and death.

CLASSIFICATION OF CARCINOGENS: METHODS AND RESPONSIBLE AGENCIES:

A carcinogen is a substance that has been scientifically proven to cause cancer in humans. There are literally hundreds of known or suspected carcinogens in the environment around us, each of them with its own unique level of risk and types of cancer-causing exposures. Cataloging large numbers of carcinogens in a scientifically meaningful way is a task that has been undertaken by numerous private and governmental organizations, though, two of the most widely recognized carcinogen classifying agencies are the International Agency for Research on Cancer (IARC), and the United States National Toxicology Program (NTP).

UNDERSTANDING CARCINOGENS:
Classifying a particular substance as a carcinogen requires a scientific understanding of the substances biological actions that cause malignant disease. This is a highly complex task that begins with the researchers knowledge of the fact that cancer occurs when the body experiences highly accelerated and uncontrolled cell division. Normal cell replication is interrupted by changes in the cells DNA, mutations that can be the result of

exposures to environmental toxins. These exposures can be behaviorally related through voluntary actions such as tobacco use or occupational in nature if (for example) an individual worked for years in an asbestos mine. Behavioral and occupational exposures to carcinogens aside, cancer-causing toxins can also exist in the air, the water, food supplies, and elsewhere.

IARC DETERMINATIONS:
As part of the World Health Organization, the IARC is responsible for the development of the most widely accepted carcinogen classification system. Over the past 30 years, the IARC has studied over 900 suspected cancercausing agents, each of which has been placed into one of the five groups that are noted below:

Group 1: Definitively proven to be carcinogenic to humans Group 2A: Most likely or probably carcinogenic to humans Group 2B: Possibly causes cancer in humans but are not assured by any experiment. Group 3: Not classifiable as a cancer causing agent in humans. They may cause cancer in other animals. Group 4: Most likely not a carcinogen in humans.

NTP CLASSIFICATIONS:
Allied with the federal Centers for Disease Control (FCDC), National Institutes of Health (NIH), and the Food and Drug Administration (FDA), the NTP issues a carcinogen classification report every two years. The NTP Report on Carcinogens classifies substances in one of the two ways noted below:

Known to be human carcinogens e.g. chromium can cause lung cancer, vinyl chloride causes liver cancer, arsenic causes skin cancer, benzene and chlorophosphate causes leukemia Reasonably anticipated to be a human carcinogen

CANCER INITIATION:
Its the first step in two stage model of cancer development. The agents that cause cancer initiation are called initiators. And the change I brings in genome by reacting with DNA is passed to the daughter cells. But for initiation of cancer 2 obstacles have to be crossed first. These are:

1. PROTO-ONCOGENE:
There are two mutational routes for uncontrolled cell proliferation and invasiveness. One of it is proto-oncogene. The proto-oncogene that functions as stimulatory gene stimulates a particular process like cell division, is mutated and made hyperactive. Secondly is to make a proto-oncogene that is working as inhibitory gene, which stops a particular process when there is no more demand of it. E.g. MYC gene.

2. Tumor Supressor Gene:

These get as a break of protein synthesis. That is TSG work as inhibitory genes and stop particular process when there is no more need of it in the cell. But on mutation it does not stops the process and synthesis goes on in uncontrolled manner. E.g. p53 gene.

3. Cell Cycle Clock:

The sequence of cell cycle events is governed by a cell cycle system, which cyclically triggers the essential process of cell reproduction such as DNA replication and chromosome segregation. At the host basic type of components, protein kinases cyclins. These complexes regulate the normal cell cycle one at a late G1 check point just before S-phase and other late in G2, just before M-phase. These protein-complexes exert control through kinase activities, which are abruptly switched on and off at particular points in cycle. The cycle is operated like a clock, allotting fixed time for each process, so if its halted in any phase or the protein complexes genes are mutated the cancer occurs.

STAGE II:
Cancer Promotion:
When all the obstacles have been crossed the cell is now mutated and start growing abnormally and makes a mass of unusual cells called tumor but still its localized to a tissue. Still its not harmful and so is called benign tumor. As its not a monolayer of cells rather a lump of cells, cells mounting on each other so they need some nutrition + O2 source directly.

ANGIOGENESIS:
New vessels always originate as capillaries, which sprout from existing small vessels. Its an important phenomenon in tumor growth. The growth of a solid tumor is limited by capillaries; a tumor would be dependent on diffusion of nutrients from its surroundings and could not enlarge beyond a diameter of a few millimeters. To grow and promote cancer, tumor induces the formation of capillary network that invades the tumor mass. The cells are supplied nutrition and O2 through these capillaries.

CANCER PROGRESSION:
Progression is associated with the invasion of tumor cells i.e. its a step from benign tumor formation to cause malignancy and the spreading of cancer is called metastasis. Metastasis: The cells of a typical solid tumor must be able to loosen their adhesion to their original neighbors, escape from the tissue of origin, burrow through other tissue until they reach a blood vessels/lymphatic vessel, cross the basal lamina and endothelial lining of vessel. So as to enter the blood circulation from there, it enters elsewhere in the body and survives and proliferates in new environment in which they find themselves.

The final steps in metastasis are probably the most difficult, many tumors release large of cells into circulation, but only a tiny proportion of these cells succeed in founding metastatic colonies. And sometime a tumor cell to metastatize requires some additional transformations / epigenetic changes.

PROGRESSION DEPENDS UPON:

Rate of progression towards malignancy depends on frequency of mutation. The mutation rate may be high because of mutagens in environment or because of intracellular defects in machinery governing replication recombination and repair of DNA defect in enzymes, etc.

1. PROTO-ONCOGENES:
Normal gene usually concerned with the regulation of cell proliferation that can be converted into a cancer promoting oncogene by mutation. Products of Proto-oncogenes: Signaling molecules; Growth factors: Cells in higher animals normally divide only when they are stimulated by growth factors which are produced by other cells and usually act by binding to receptor tyrosin kinase. Cancer cells proliferate excessive, mainly because they are able to divide without stimulation from other cells and therefore are no longer subject to the normal social controls on cell proliferation mutation affect genes that encode for proteins involved in signaling pathways. e.g. Ras, Scr, Raf, Fos and jun were first identified as mutant forms in cancer cells e.g. Sis-gene, Int-2-4m lec!

2. GROWTH FACTOR RECEPTORS:

Proto-oncogenes also encode for growth factor receptor. Abnormal expression of these genes i.e. the conversion of them into sis-oncogenes and expression of suppose a receptor; (i) PDGF and continuously stimulate the cell to proliferate by growth factor. (ii) eroB gene encodes a truncated from of the EGF receptor that has an intracellular tyrosine kinase domain that is continuously active. Cells expressing this oncogene behave as they are constantly being signaled to proliferate by a growth factor.

3. SIGNAL TRANSDUCERS:
An extracellular / intracellular molecule that cues the response of a cell to the behavior of other cells / objects in the environment is called signal transducer. These are also product of proto-oncogenes and continuously take part in the integration of cells and thus the cellular process. The cell is signaled to divide and proliferate and when its divided upto the need the signal is switched off.

PROTEIN SERINE / THREONINE KINASES:

They can be activated as oncogenes by either abnormal expression / deletion of regulatory domains. These kinases include Raf and members of protein kinase family, which function as downstream effectors in signal transduction pathway initiated by binding of Growth factor to the receptors. Raf in particular play a central role in signal transduction from protein-tyrosine kinase receptor, being activated a protein kinase cascade that ultimately triggers cell proliferation.

4. TRANSCRIPTION FACTORS:
Transcription of Eu-genes is controlled by interaction of proteins, called transcription factors with specific regulatory DNA sequences. i. Jun Gene: encodes a group of related transcription factors that regulate expression of growth factors. ii. Fos Gene: encodes a protein that binds to regulatory sequence of a gene which is transcribed during adipocyte differentiation. iii. Myb Gene: Its a Transcription activator activation of Myb as oncogene require deletion of sequences at either at amino / carboxy terminals.

5. APOPTOTIC FACTORS:
Those proteins that are involved in driving the process of programmed cell death are called Apoptotic factors. Cell death is as important as cell division in generating an individual with the right cell types in the right places. E.g. ced-3, ced-4: These are 2 genes responsible for making apoptotic factors in CE lagans. (Ced stands for cell death abnormal). If either gene is inactivated by mutation, the cells that are normally fail to die survive instead and keep dividing.