MICROTUBULE: A NOVEL TARGET FOR CANCER THERAPY

For cancer therapy, microtubule network is an attractive cellular target. Main component of cell cycle is mitotic stage, particularly when the mitotic spindle separates the replicated chromosomes. The rapid microtubule dynamics also play a critical role for activities of the bipolar spindle. Microtubule targeting drugs act at binding site either by destabilizing or hyper-stabilizing microtubules. It results mitotic arrest at the prometaphase or metaphase to anaphase transition, then it leads to subsequent apoptotic cell death. Taxanes and Vinca alkaloids have been validated by the successful use for a wide variety of human cancer. Clinical development of colchicines for cancer therapy has not been successful till now because they produce toxic effect in normal tissues. Semi-synthetic analogue of taxane, docetaxal is more potent than paclitaxel against cancer cell proliferation. It is now used for the treatment of breast, prostate and non small cell lung cancer. Successful use of paclitaxel and docetaxel in cancer therapy has inspired the new microtubule targeting agents that bind to taxane site, like Epothilones, discodermolide, eleuthelobin, sarcodictyins are under clinical investigation. New treatment options are available to patient with metastatic breast cancer in the form of a new drug class – epothilone. But only ixabepilone from epothilones class is currently approved by the US. This review is specifically devoted to microtubules and their implications to cancer therapy