Anti- CANCER drugs Dr. Mohammed Abd-Almoneim

Treatment of Cancer Surgery to remove solid tumors Radiation to kill cancer cells that have spread to adjacent local or regional tissues Chemotherapy to kill cancer cells located throughout the body

Treatment of cancer There are three main approaches to treating established cancer: Surgery, Radiation therapy, Chemotherapy Breast cancer Surgery Radiation Chemotherapy Chemotherapy of cancer presents a difficult problem. In biochemical terms, cancer cells and normal cells are so similar in most respects that it is more difficult to find differences between them.

Classifications of Anti- CANCER drugs According to mechanism:   1-Alkylating agents: Example: nitrogen mustard and cyclophosphamide. Mechanism: bind irreversibly to macromolecules in the cell as DNA, RNA and proteins. 2-Antimetabolites:   Mechanism: these are closely related analogues of normal components intermediary metabolism or DNA synthesis. Example: Methotrexate inhibits folic acid metabolism. 6-mercaptopurine inhibit DNA synthesis.

3-Natural products: A wide range of drugs has been developed from plants, bacteria, yeasts and fungi. Examples and mechanisms: Mitosis inhibitors: as vincristine . Antibiotics: as actinomycin D.   4-Steroid hormones and antihormones: Examples: prednisolone, tamoxifen and cyproterone acetate. 5-Others: Several drugs have been identified, Mechanism of action is not fully established but are thought to interact with DNA synthesis or replication. They include , dacarbazine, and cis-platinum.

Alkylating Agents One of the frightening developments of World War I was the introduction of chemical warfare. The nitrogen mustards were observed to inhibit cell growth, especially of bone marrow. Shortly after the war, these compounds were investigated and shown to inhibit the growth of cancer cells.

Alkylating Agents Mechanism of Action Nitrogen mustards inhibit cell reproduction by binding irreversibly with the nucleic acids (DNA). The specific type of chemical bonding involved is alkylation. After alkylation, DNA is unable to replicate and therefore can no longer synthesize proteins and other essential cell metabolites. Consequently, cell reproduction is inhibited and the cell eventually dies from the inability to maintain its metabolic functions.

Antimetabolites (Folic Acid Antagonist) Methotrexate （MTX） Mechanism of Action： The structures of MTX and folic acid are similar. MTX is actively transported into mammalian cells and inhibits dihydrofolate reductase, the enzyme that normally converts dietary folate to the tetrahydrofolate form required for thymidine and purine synthesis.

Hormones Several types of hormone-dependent cancer (especially breast, prostate, and endometrial cancer) respond to treatment with their corresponding hormone antagonists. Estrogen antagonists are primarily used in the treatment of breast cancer (tamoifen) Tamoxifen is the drug of choice in postmenopausal women with or recovering from metastatic breast cancer. It is most effective in patients who have estrogen receptor-positive tumors. whereas androgen antagonists are used in the treatment of prostate cancer (cyproterone acetate). Corticosteroids (predinsolone) are particularly useful in treating lymphocytic leukemias and lymphomas.

Problems With Cancer Chemotherapy Drug Resistance. Drug Toxicity.

Adverse effects: A- general:   A- general: Reactions to cancer chemotherapy are secondary to cell death both in the tumor and in other rapidly dividing cells of bone marrow, gastrointestinal tract, germinal epithelium etc.

1-Nausea and vomiting:   related to the direct actions of cytotoxic drugs on the chemoreceptor trigger zone or secondary to extensive tissue damage as occurs in radiation sickness.   Metoclopramide (antiemetics) and the cannabinoid nabilone can be used to control nausea and vomiting.  2-Alopecia:   is a common adverse effect of cytotoxic drugs. Hair re-grows after the drugs are withdrawn.

4-Hyperuricaemia:   Very high levels of plasma uric acid with precipitation of clinical gout or renal failure may complicate treatment of leukaemias and Iymphomas. Allopurinol, the xanthine oxidase inhibitor, may be used to prevent gout. 5-Diarrhoea and malabsorption: occur as a result of cytotoxic effects on gut mucosal cell turnover.

6-Bone marrow depression:   The bone marrow is particularly sensitive to cytotoxic drugs. Neutropenia or thrombocytopenia is common. They result in an increased risk of infection and haemorrhage respectively. 7-Opportunistic infections: occur as a result of neutropenia and immunosuppressant therapy, which interfere with humoral and cell-mediated responses. Unusual infection with fungi and protozoa in addition to common pathogenic bacteria and viruses occur.

B. Specific adverse effects Cyclophosphamide :haematuria, cystitis Doxorubicin : cardiotoxic, alopecia. Bleomycin : pulmonary fibrosis. Methotrexate: marrow suppression, megaloblastic anaemia. Vincristine: peripheral neuropathy. Cisplatinum: Renal damage.

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