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Cancer Chemotherapy – I

Cancer Chemotherapy – I. Dr. Nasir Ali Afsar MBBS, M.Phil , Ph.D. Senior Lecturer of Pharmacology. WHO Report: Global Leading Causes of Death, 2004. www.who.int/healthinfo/global_burden_disease/2004_report_update/en/index.html. What is a neoplasm?. Neo + plasm = new growth

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Cancer Chemotherapy – I

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  1. Cancer Chemotherapy – I Dr. Nasir Ali AfsarMBBS, M.Phil, Ph.D. Senior Lecturer of Pharmacology

  2. WHO Report: Global Leading Causes of Death, 2004 www.who.int/healthinfo/global_burden_disease/2004_report_update/en/index.html

  3. What is a neoplasm? • Neo + plasm = new growth • Loss of responsiveness to normal growth control: • Origin: • Single germ layer • Monoclonic (mostly) • Pleomorphic • Multiple germ layers = teratoma • May be benign or malignant (cancer)

  4. What is a neoplasm? • Signs of Malignancy: • Higher rate of growth • Poor differentiation • Invasion • Local • Distant (metastasis)

  5. Physiology of Cell Proliferation 2nd messenger Growth Factor • REGULATORY GENES • Proto-oncogenes: growth promoting • Anti-oncogenes:Rb, p53 • Apoptosis regulating genes: p53, bcl-2 • DNA repair genes

  6. Genesis of Cancer Altered Gene Expression Overexpression of proto-oncogenes/ Decreased expression of tumor suppressor genes Tumor Development Clonal diversification through additional… Genetic Mutations Inherited/ Acquired Invasion/ Metastasis

  7. Approaches to Cancer Therapy • Remove - Surgery • Kill • ‘Carpet’ bombing, indiscriminate • Radiotherapy • Chemotherapy • Angiogenesis inhibitors • ‘Target’ killing • Immunotherapy • ‘Radical’ recovery • Gene Therapy • Self sufficiency • Response modifiers: ILs, IFN, GFs.

  8. Classification of Chemotherapeutic Agents • Cytotoxic drugs • Alkylating agents and related comp. • Antimetabolites • Natural products • Hormones • Immunoglobulins • Miscellaneous

  9. Alkylating Agents and Related Compounds • Nitrogen mustards • Mechlorethamine • Cyclophosphamide & Ifosfamide • Melphalan • Chlorambucil • Ethylenimines & methylmelamines • Thiotepa • Alkylsulfonates • Busulfan • Nitrosoureas • Carmustine, Lomustine, Semustine • Streptozocin • Triazenes • Dacarbazine, Procarbazine Note: The drugs marked blue are those included in prescribed drug list by the relevant discipline.

  10. Antimetabolites • Purine analogs • 6-Mercaptopurine & Azathioprine • Thioguanine • Fludarabine & Cladribine • Pentostatin • Pyrimidine analogs • 5-FU & Floxuridine • Ara C • Gemcitabine • Folate analogs • Methotrexate (MTX) Note: The drugs marked blue are those included in prescribed drug list by the relevant discipline.

  11. Natural Anticancer Products • Antibiotics • Actinomycin D • Anthracyclins (Doxorubicin, Daunorubicin, Epirubicin, Idarubicin) • Bleomycin • Mitomycin • Enzymes • L-Asparaginase • Antimitotic drugs • Vincaalkaloids • paclitaxel • Topoisomerase-I inhibitors • Campothecinanalogs (Topotecan, Irinotecan) • Topoisomerase-II inhibitors • Epipodophyllotoxins(Etoposide, Teniposide) Note: The drugs marked blue are those included in prescribed drug list by the relevant discipline.

  12. Hormones • GnRH Analogues: Leuprolide (Prostate) • Estrogens: DES, Ethinylesterdiol(Breast, Prostate) • Antiestrogens: Tamoxifen(Breast) • Progestins: Hydroxyprogestrone (Endometrium, Breast) • Androgens: Testosterone (Breast) • Antiandrogens: Flutamide(Prostate) • Adrenocortical Steroids: Prednisone. (Lukemias, Lymphomas, Breast) • Adrenocortical Suppressant: Mitotane, Aminoglutethimide. (Adrenal Cortex) Note: The drugs marked blue are those included in prescribed drug list by the relevant discipline.

  13. Antibodies and TKIs Imatinib(CML) Trastuzumab(Breast) Cetuximab(Colorectal) Bevacizumab(Colorectal, Lung) Note: The drugs marked blue are those included in prescribed drug list by the relevant discipline.

  14. Miscellaneous Chemotherapeutic Agents • Cisplatin, Carboplatin • Hydroxyurea • Procarbazine • Mitotane

  15. The Cell Cycle Specificity of Anticancer Drugs Cell Cycle Non-specific: Acts during all phases, G1, S, G2, M and G0 Example: Alkylating agents Cell Cycle Specific: Acts during active cell cycle; not during G0 Example: Anthracyclines Physiological checkpoints Phase Specific: Acts only during a specific phase Example: as shown

  16. Site of Anticancer Action Immuno-globulins, TKIs, Hormones Vinca alkaloids, Taxanes Anti-metabolites Anti-metabolites http://img.docstoccdn.com/thumb/orig/123224052.png Alkylating Agent and Platinum compounds Blood Vessel Anthracyclines, Bleomycin, Etoposide Asparaginase

  17. Site of Anticancer Action: in Nucleus Lippincott’s Pharmacology, 5e

  18. THANK YOU • Disclaimer: This presentation is only an adjunct to the prescribed Pharmacology textbooks. • REFERENCES • Goodman & Gilman’s Pharmacological Basis of Therapeutics. Ed. 12 • Pharmacology: by Range, Dale & Ritter. Ed. 7 • Katzung’s Basic and Clinical Pharmacology. Ed. 12 • http://emedicine.medscape.com • www.dhs.sa.gov.au

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