Anticancer Drugs : Definition, Classification, Example, Mechanism of Action
- Anticancer drugs either kill cancer cells or modify their growth. However, selectivity of majority of drugs is limited and they are one of the most toxic drugs used in therapy.
A. Cytotoxic drugs (Drugs acting directly on cells)
1. Alkylating agents
- Mechanism of action: They produce highly reactive carbonium ion intermediates which transfer alkyl groups to cellular macromolecules by forming covalent bonds. Alkylation results in cross linking/ abnormal base pairing/ scission of DNA strand. Cross linking of nucleic acids with proteins can also take place.
- The position 7 of guanine residues in DNA is especially susceptible, but other molecular sites are also involved.
- They have cytotoxic and radiomimetic (like ionizing radiation) actions.
- Many of them are cell cycle non-specific, i.e. act on dividing as well as resting cells.
- Some have CNS stimulant and cholinergic properties.
- These are analogues related to normal components of DNA or of coenzymes involved in nucleic acid synthesis.
- They competitively inhibit utilization of the normal substrate or get themselves incorporated forming dysfunctional macromolecules.
Folate antagonists Purine antagonists Pyrimidine antagonists Cytidine antagonists Methotrexate (Mtx) 6-Mercaptopurine (6-MP) 5-Fluorouracil (5-FU) Gemcitabine Pemetrexed 6-Thioguanine (6-TG) Azathioprine Cytarabine (cytosine arabinoside) Pralatrexate Fludarabine Capecitabine Cladribine Azacitidine
- These are products obtained from microorganisms and have prominent anti-tumour activity.
- Practically all of them intercalate between DNA strands and interfere with its template function.
Actinomycin D (Dactinomycin)
4. Microtubule Inhibitors
Vincristine / Oncovine
5. Monoclonal Antibodies
6. Tyrosine Kinase Inhibitors
B. Drugs altering hormonal milieu
- They have marked lympholytic action-are primarily used in acute child- hood leukaemia and lymphomas.
- E.g. Prednisolone
- They produce symptomatic relief in carcinoma prostate, which is an androgen-dependent tumour.
- E.g. Fosfestrol, Ethinylestradiol
3. Selective estrogen receptor modulators
- E.g. Tamoxifen, Toremifene
4. Selective estrogen receptor down regulators
- E.g. Fulvestrant, Raloxifene
5. Aromatase inhibitors
- E.g. Letrozole, Anastrozole, Exemestane
- E.g. Flutamide, Bicalutamide, Nilutamide
7. 5-α reductase inhibitors
- E.g. Finasteride, Dutasteride
8. Gn RH analouges
- E.g. Hydroxyprogesterone acetate, Megestrol acetate