Chemotherapy

Chemotherapy

1. Prabhudas N. Molecular basis of chemotherapy

2. Paul E hrlich (1854 – 1915) German scientist and also father of chemotherapy Contributions: Salvarsan compound “ magic bullet ” concept and also neosalvarsan methods of standardizing toxin and antitoxin stains to the cells and tissues Acid –fast stain in nature “ Side chain theor y” of antibody production

3. CHEMOTHERAPY Systemic therapy is the main treatment available for disseminated malignant tumor . Progress in chemotherapy result in cure for several tumors . Chemotherapy usually given by drugs in a multiple cycles. Medications that destroy cancer cells There are over 100 different chemo drugs One or more chemo drugs may be used to treat different cancer .

4. Chemotherapy involves the use of chemicals to treat cancer. Chemotherapeutics are cytotoxic drugs that mainly target dividing cells. Therefore chemotherapy also affects cells that divide rapidly under normal fashion. This includes, progenitor cells in the bone marrow,  digestive tract, and hair follicles. This results in the most common side-effects of chemotherapy:  myelosuppression (decreased production of blood cells, hence also  immunosuppression)   mucositis (inflammation of the lining of the digestive tract ) alopecia  (hair loss )

5. Chemotherapy drug given by Adjuvant chemotherapy: Chemotherapy given after surgery or irradiation to destroy micrometastasis & prevent development of secondary neoplasm. Neo-adjuvant chemotherapy: Chemotherapy given before surgery or radiotherapy in order to diminish the volume of large primary neoplasm. Chemotherapeutic agents may be classified into 4 groups: Alkylating agents Antimetabolite Anti-microtubule agent Cytotoxic antibiotics

6. Alkylating agent: An  alkylating antineoplastic agent  is substance used in cancer treatment that attaches an alkyl group (C n H 2n+1 ) to DNA. The alkyl group is attached to the guanine base of DNA, at the number 7 nitrogen atom of the  purine  ring. Cancer cells are more sensitive to alkylation than normal cells, as their DNA repair system is inefficient. Most of the alkylating agents are also  carcinogenic . Example: Cyclophospamide , Busulfan .

7. Purine ring 7 position

8. Cisplatin : Cisplatin is a chemotherapeutic drug that binds to guanine residues in the DNA and cause either intra or inter-strand crosslink. It is called an alkylating -like compound as it crosslinks DNA but does not contain an alkyl group. The crosslinks can potential block DNA replication. Therefore, DNA repair system is activated to remove it. When removal of DNA lesion is impossible or incomplete, cell death by apoptosis is induced. Thus, cisplatin removes cancer cell by inducing apoptosis.

9. Antimetabolite: These are compounds that inhibit a metabolite from participating in a biochemical process. Antimetabolites are structurally similar to the natural metabolites and are therefore called analogs. These compounds thus block the functioning of biochemical reactions and pathways. Example: 5FU, 6 marcoptopurine and methotrexative

10. Paclitaxel ( Taxol ) This is an antineoplastic alkaloid obtained from the bark of the tree Taxus brevifolia . Paclitaxel is one of several  cytoskeletal drugs  that target  tubulin . Paclitaxel-treated cells have defects in mitotic spindle assembly, chromosome segregation, and cell division. Unlike other tubulin-targeting drugs such as  colchicine  that inhibit microtubule assembly, paclitaxel stabilizes the  microtubule  polymer and protects it from disassembly. Chromosomes are thus unable to achieve a metaphase spindle configuration. This blocks progression of mitosis, and prolonged activation of the mitotic checkpoint triggers apoptosis or reversion to the G-phase of the cell cycle without cell division

11. Goals of chemotherapy Eliminate the cancer Shrink the tumor Prevent cancer from spreading Relieve symptoms from cancer, such as pain