Alkylating agents and cancer therapy

Alkylating agents have been used for the treatment of cancer for over six decades, yet their repertoire continues to grow. These agents act during all phases of the cell cycle, directly on DNA, crosslinking the N-7-guanine residues, causing DNA strand breaks, leading to abnormal base pairing, inhibition of cell division and eventually resulting in cell death. Their systemic toxicity and drug resistance are major obstacles in limiting their clinical efficacy. Major thrust is being laid on discovery of combinations of alkylating agents with other anticancer agents or inhibitors of DNA repair enzymes, topoisomerases, COX-2, p34(cdc2) kinase, phosphatases, multi-drug resistance proteins and antivascular agents for improving their clinical efficacy. In addition, novel modulators, such as naphthalimides and their analogues and selective androgen receptor modulators, are being developed to increase the sensitivity of cancer cells to alkylating anticancer agents. This review focuses on patents published during 2005 - 2006 on alkylating anticancer agents.