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Alkylating agents

Abstract : With the approval of mechlorethamine by the FDA in 1949 for the treatment of hematologic malignancies, alkylating agents are the oldest class of anticancer agents. Even though their clinical use is far beyond the use of new targeted therapies, they still occupy a major place in specific indications and sometimes represent the unique option for the treatment of refractory diseases. Here, we are reviewing the major classes of alkylating agents and their mechanism of action, with a particular emphasis for the new generations of alkylating agents. As for most of the chemotherapeutic agents used in the clinic, these compounds are derived from natural sources. With a complex but original mechanism of action, they represent new interesting alternatives for the clinicians, especially for tumors that are resistant to conventional DNA damaging agents. We also briefly describe the different strategies that have been or are currently developed to potentiate the use of classical alkylating agents, especially the inhibition of pathways that are involved in the repair of DNA lesions induced by these agents. In this line, the development of PARP inhibitors is a striking example of the recent regain of interest towards the "old" alkylating agents.
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Contributor : Philippe Pourquier Connect in order to contact the contributor
Submitted on : Tuesday, January 14, 2020 - 1:24:41 PM
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Philippe Pourquier. Alkylating agents. Bulletin du Cancer, John Libbey Eurotext, 2011, 98 (11), pp.1237-1251. ⟨10.1684/bdc.2011.1471⟩. ⟨inserm-02438826⟩



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