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Directly targeting the mitochondrial pathway of apoptosis for cancer therapy using BH 3 mimetics – recent successes, current challenges and future promise
Author(s) -
Sarosiek Kristopher A.,
Letai Anthony
Publication year - 2016
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.13714
Subject(s) - apoptosis , cancer , cancer research , bcl 2 family , cancer cell , biology , programmed cell death , biochemistry , genetics
Apoptosis within cancer cells is controlled by the BCL ‐2 family of proteins, making them powerful arbiters of cell fate in response to stress induced by neoplastic transformation as well as exposure to anti‐cancer therapies. Many cancers evade pro‐apoptotic stress signals by up‐regulating anti‐apoptotic proteins such as BCL ‐2, BCL ‐ X L or MCL ‐1 to maintain their survival. However, this may come at a cost, as these cancers may also become dependent on these anti‐apoptotic proteins for survival. The development and deployment of BCL ‐2 family inhibitors (drugs that mimic the activity of pro‐apoptotic BH 3‐only proteins or ‘ BH 3 mimetics’) is based on this paradigm, and the first potent and specific molecules are now being evaluated in clinical trials. We review the recent successes in this field, the challenges currently being faced, and the promising future ahead.