Mitochondriotoxic compounds for cancer therapy.
One of the hallmarks of cancer cells is their increased resistance to apoptosis induction. Alterations in many apoptosis regulators belonging to the intrinsic pathway confer emerging neoplastic cells with a selective growth advantage in the hostile tumor microenvironment. The realization that those same defects contribute to resistance to radiation and chemotherapeutic agents have prompted the unrelenting search for mitochondria-targeted compounds for the treatment of cancer. Mitochondria play a central role in the process of cell death. They serve as integrators of upstream effector mechanisms. Most importantly, mitochondrial outer membrane permeabilization becomes a commitment point during cell death. Thus, strategies aimed at directly triggering this event by either blocking the activity of antiapoptotic factors or by interfering with vital mitochondrial functions may help to overcome resistance to standard cancer therapy.
Fantin
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Merck & Co. Inc., Boston, MA, USA. valeria_fantin@merck.com
Leder
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D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004272:DNA, Mitochondrial / Q000187:drug effects; D006801:Humans; D008928:Mitochondria / Q000187:drug effects*; D009369:Neoplasms / Q000188:drug therapy*
D000970:Antineoplastic Agents; D004272:DNA, Mitochondrial