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Antineoplastic Agents

Antineoplastic Agents.

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Antineoplastic Agents

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  1. Antineoplastic Agents The main goal of antineoplastic agents is to eliminate the cancer cells without affecting normal tissues (the concept of differential sensitivity).  In reality, all cytotoxic drugs affect normal tissues as well as malignancies - aim for a favorable therapeutic index (aka therapeutic ratio). Two Major Classes Cancer Chemotherapy Chapter 55. B.G. Katzung

  2. Cell Cycle and Cancer. Normal and Cancer cells must traverse before and during cell division. Differentiation 2% Synthesis of cellular Components needed For Mitosis 19% Synthesis of cellular Components needed For DNA synthesis. Replication of DNA genome 40% 39% Cancer Chemotherapy Chapter 55. B.G. Katzung

  3. Cancer Chemotherapy Chapter 55. B.G. Katzung

  4. Structure of Major Alkylating Agents

  5. Alkylating Agents: General Mechanism of Action E.g., Mechlorethamine (Nitrogen Mustards) Cancer Chemotherapy Chapter 55. B.G. Katzung

  6. Cyclophosphamide (Alkylating agent) Inactive Aldophosphamide 4-Hydroxycyclophamide Breast, ovarian, CLL, soft tissue sarcoma, WT, neuroblastoma Cancer Chemotherapy Chapter 55. B.G. Katzung

  7. A. Alkylating agents

  8. A. Alkylating agents

  9. A. Alkylating agents

  10. Summary Cancer Chemotherapy Chapter 55. B.G. Katzung

  11. B. Natural Products 1. Antimitotic Drugs 2. Antimitotic Drugs

  12. 3. Epipodophyllotoxins (These are CCS) Act on Topoisomerase II Accumulation of single- or double-strand DNA breaks, the inhibition of DNA replication and transcription, and apoptotic cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle

  13. 4. Antibiotics Cancer Chemotherapy Chapter 55. B.G. Katzung

  14. 5. Enzymes: L-asparaginase Cancer Chemotherapy Chapter 55. B.G. Katzung

  15. C. Antimetabolites (Folic acid analog) MTX polyglutamates Are selectively retained In tumor cells. Folic acid is an essential dietary factor, from which THF cofactors are formed which provide single carbon groups for the synthesis of precursors of DNA and RNA. To function as a cofactor folate must be reduced by DHFR to THF. Reduced Folate Carrier protein Methotrexate Kills cells during S-phase Cancer Chemotherapy Chapter 55. B.G. Katzung

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