Anti-Cancer

Treatment of Cancer

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

There are 3 main approaches to treating established cancer: 

Surgery, Radiation therapy, 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.

Advances in Cancer Chemotherapy

Treatment options of cancer:

• •Surgery: before 1955
• •Radiotherapy: 1955~1965
• •Chemotherapy: after 1965
• •Immunotherapy, biological therapy and Gene therapy

Classifications of Anti-Cancer drugs According to mechanism:

1. Alkylating agents: Mechanism: bind irreversibly to macromolecules in the cell as DNA, RNA and proteins. Example:  nitrogen mustard; leukemia, lymphoma and cyclophosphamide.

2. Anti-metabolites:  (Folic Acid Antagonist) 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; severe irreversible peripheral neuropathy. Antibiotics: as actinomycin D.

4. Steroid hormones and antihormones:  Examples:  prednisolone, tamoxifen and cyproterone acetate.

5. OthersY: 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.

Biological therapyR

These agents specifically target molecular anomalies in signal transduction pathways that exist in tumor cells.

As biological agents target pathways which are more critical to cancer cells than normal cells they are generally less toxic than chemotherapy and in some cases are more effective.

Example: monoclonal antibodies

Problems With Cancer Chemotherapy

Drug Resistance. & Drug Toxicity

Adverse effects:

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.

3. 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.

4. Diarrhoea and malabsorption:  occur as a result of cytotoxic effects on gut mucosal cell turnover.

5. 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.

6. 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:

• anti-alkylating agents Cyclophosphamide: haematuria, cystitis = urinary incontinence

• Doxorubicin : cardiotoxic, alopecia.

• Bleomycin : pulmonary fibrosis.

• Folic acid antagonist/ anti-metabolite Methotrexate: marrow suppression, megaloblastic anaemia.

• Natural products - mitosis inhibitors Vincristine: peripheral neuropathy.

• Cisplatinum: Renal damage.