title: The BCL2 Family: Key Mediators of the Apoptotic Response to Targeted Anticancer Therapeutics.
abstract: The ability of cancer cells to suppress apoptosis is critical for carcinogenesis. The BCL2 family proteins comprise the sentinel network that regulates the mitochondrial or intrinsic apoptotic response. Recent advances in our understanding of apoptotic signaling pathways have enabled methods to identify cancers that are "primed" to undergo apoptosis, and have revealed potential biomarkers that may predict which cancers will undergo apoptosis in response to specific therapies. Complementary efforts have focused on developing novel drugs that directly target antiapoptotic BCL2 family proteins. In this review, we summarize the current knowledge of the role of BCL2 family members in cancer development and response to therapy, focusing on targeted therapeutics, recent progress in the development of apoptotic biomarkers, and therapeutic strategies designed to overcome deficiencies in apoptosis.
  
  
  CONCLUSIONS
  Apoptosis, long known to be important for response to conventional cytotoxic chemotherapy, has more recently been shown to be essential for the efficacy of targeted therapies. Approaches that increase the likelihood of a cancer to undergo apoptosis following therapy may help improve targeted treatment strategies. Cancer Discov; 5(5); 475-87. ©2015 AACR.
authors.affiliation: Massachusetts General Hospital Cancer Center, Charlestown, Massachusetts. Department of Medicine, Harvard Medical School, Boston, Massachusetts.
authors.forename: Aaron N
authors.initials: AN
authors.lastname: Hata
authors.affiliation: Massachusetts General Hospital Cancer Center, Charlestown, Massachusetts. Department of Medicine, Harvard Medical School, Boston, Massachusetts. jengelman@partners.org acfaber@vcu.edu.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Engelman
authors.affiliation: Virginia Commonwealth University Philips Institute for Oral Health Research, School of Dentistry and Massey Cancer Center, Richmond, Virginia. jengelman@partners.org acfaber@vcu.edu.
authors.forename: Anthony C
authors.initials: AC
authors.lastname: Faber
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D000072224:Bcl-2-Like Protein 11; D015415:Biomarkers; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000628:therapy; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; D015415:Biomarkers; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2