Introduction to antineoplastic agents.pptx

Introduction to Antineoplastic agents

1. ANTINEOPLASTIC AGENTS Dr. Navidha MMCP, MMDU

2. INTRODUCTION Cancer is a term used for diseases in which abnormal cells divide without control and are able to invade other tissues. Cancer cells can spread to other parts of the body through the blood and lymph systems. Cancer is not just one disease but many diseases. There are more than 100 different types of cancer. Most cancers are named for the organ or type of cell in which they start - for example, cancer that begins in the colon is called colon cancer; cancer that begins in melanocytes of the skin is called melanoma.

3. Along with heart disease, cancer is the largest cause of death in the developed world. Cancer affects 1 in 3 people and is responsible for 25% of all deaths. Cancer is an unregulated proliferation of cells due to loss of normal controls, resulting in unregulated growth, lack of differentiation, local tissue invasion, and, often, metastasis. Cancer can develop in any tissue or organ at any age. There is often an immune response to tumor. Many cancers are curable if detected at an early stage.

4. Types of cancer Carcinoma- cancer that begins in the skin or in tissues that line or cover internal organs. There are a number of subtypes of carcinoma, including adenocarcinoma, basal cell carcinoma, squamous cell carcinoma, and transitional cell carcinoma. Sarcoma- cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukaemia- cancer that starts in blood-forming tissue such as the bone marrow and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and myeloma- cancers that begin in the cells of the immune system. Central nervous system cancers - cancers that begin in the tissues of the brain and spinal cord.

5. Not all tumors are cancerous; tumors can be benign or malignant. Benign tumors aren't cancerous . They can often be removed, and, in most cases, they do not come back. Cells in benign tumors do not spread to other parts of the body. Malignant tumors are cancerous. Cells in these tumors can invade nearby tissues and spread to other parts of the body. The spread of cancer from one part of the body to another is called metastasis. Some cancers do not form tumors. For example, leukaemia is a cancer of the bone marrow and blood .

6. ETIOLOGY OF CANCER 1.GENETIC MUTATIONS are largely responsible for the generation of malignant cells. Two major categories of mutated genes are oncogenes and tumor suppressive genes. ONCOGENES- These are the abnormal form of normal genes that are called proto-oncogenes, regulating cell growth. Mutations of these genes result in direct and continuous stimulation of molecular biological pathways for cancer that control cell growth and division. For example- RAS gene encodes for cell growth and division. Mutations in the gene leads inappropriate cell growth and division.

7. TUMOR SUPRESSIVE GENES- Tumor suppressor genes are inherent genes that play important role in cell division and DNA and are critical in detecting inappropriate growth signals in the cell. If the genes as a result of inherited or acquired mutation become unable to function, genetic mutations of the genes can proceed unchecked, leading to noeplastic transformations. Another important protein p53 prevents replication of DNA in normal cell and promotes cell death(apoptosis) in cells with abnormal DNA. Inactive or altered p53 allows cells with abnormal DNA to survive and divide.

8. Telomeres are nucleoprotein complexes that cap the ends of chromosomes and maintain their integrity. Telomere shortening occur with aging .Telomerase is an enzyme that provides for telomere synthesis and maintenance, thus telomerase may potentially allow for cellular immortality . Telomerase activity may promote tumors through multiple, complex mechanisms, especially by subverting the normal DNA synthetic checkpoints. 2.VIRUSES- Viruses contribute to the pathogenesis of human malignancies through the integration of viral genetic elements into the host DNA. These new genes are expressed by the host; they may affect cell growth or division, or disrupt normal host genes required for control of cell growth and division. Alternatively, viral infection may result in immune dysfunction, leading to decreased immune surveillance for early tumors. E.G. - nasopharyngeal carcinoma -Hepatitis B virus.

9. Carcinogenesis can result from ionizing radiation and may develop from 2 different mechanisms. 1. Direct ionization – damages DNA and other molecules can cause direct somatic mutations. 2. Secondary effectors such as oxygen radicals can be formed by interaction with ionizing radiation. Oxygen free radicals can damage and kill cells and also induce mutations . 5.CHEMICAL CARCINOGENS- 4.RADIATION- Arsenic and certain Arsenic compounds (e.g.. Pesticides, wood preservatives, alloying additive, glass.) Asbestos (e.g...insulation,plastics,gasketing,coating) Benzene (e.g.... solvent, gasoline additives) Mustard gas (e.g... biological studies, weapons) 2-Napthylamine (e.g.... Dyes. rubber) Vinyl chlorides (e.g... Wrapping films, credit cards, phonographic records, floor tiles) Thorium dioxide (e.g... flame sparing, welding electrodes, high temperature ceramics)

10. ACTIVATING INVASION AND METASTATIS Tumor cells escape from the primary site and disseminate into distant organs and involves changes in the way cells attach to other cells and to the extracellular matrix. This process has several steps, including- Local tissue invasion. Intravasation. Transition through the blood and lymphatic system Colonization of foreign tissue .

11. One example of this is the involvement of tumor-associated macrophages (TAMs) that supply cancer cells with epidermal growth factor (EGF) and colony-stimulating factor 1 (CSF-1) and assist with intravasation .

12. ENABLING REPLICATIVE IMMORTALITY Normal cells have a finite replicative ability. Cancer cells overcome this by over expressing telomerase, an enzyme that maintains telomere length, which protects the ends of chromosomes and allows the cell to continue proliferating. This process is also aided in part by the loss of tumor suppressor genes such as p53.

13. EVADING CELL PROLIFIRATION Cancer cells circumvent normal growth suppressors in order to continue proliferation   2 tumor suppressors most commonly deregulated in cancer cells are retinoblastoma protein ( Rb ) and p53.   Rb actively inhibits cell passage through the restriction point in the G 1  cell cycle phase Cancer cells with mutated Rb remove this gatekeeper and allow for ongoing cell proliferation p53 functions as a central regulator of apoptosis because it arrests the cell cycle in cells with DNA damage Loss of p53 allows for cell cycle progression despite DNA damage and cellular stresses

14. EVADING IMMUNE DESTRUCTION Immune surveillance is an essential cellular process that proactively prevents tumor formation in the human body Cancer immuno editing, includes 3 key phases ELIMINATION PHASE IMMUNE SYSTEM RECOGINSE AND ELIMINATES CANCER CELLS EQUILIBRIUM PHASE TUMOR CELLS ARE NOT COMPLETELY ELIMINATED BUT THEIR GROWTH IS CONTROLED BY IMUUNE SYSTEM ESCAPE PHASE TUMOR CELLS NOT DETECTED,DESTROYED BY IMMUNE SYSTEM,CONTINUE TO DIVIDE AND GROW

15. INDUCING ANGEOGENESIS The moment at which a tumor begins to over express pro-angiogenic factors, such as vascular endothelial growth factor (VEGF), is generally referred to as the “angiogenic switch .” Unabated angiogenesis enables tumor expansion and local invasion through . Delivery of oxygen and nutrients Production of growth factors that benefit tumor cells.