Restoring cancer's death sentence.
In this issue of Cancer Cell, two groups present data on the function of an antagonist of BCL-2, ABT-737. Both groups find that expression of MCL-1, an antiapoptotic protein related to BCL-2, is a key determinant of resistance to ABT-737. Lowering MCL-1 levels is an effective adjunct to BCL-2 antagonism, and both groups suggest ways that this might be accomplished practically in a clinical setting. The mechanism by which ABT-737 selectively kills cancer cells is discussed below in the context of these and prior reports of ABT-737's function. Antagonism of BCL-2 is an exciting anticancer strategy that may soon become a clinical reality.
Letai
Anthony
A
Department of Medical Oncology, Dana-Farber Cancer Institute, 44 Binney Street, Dana 530B, Boston, Massachusetts 02115, USA. anthony_letai@dfci.harvard.edu
D000818:Animals; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D006801:Humans; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D009596:Nitrophenols / Q000627:therapeutic use*; D010879:Piperazines / Q000627:therapeutic use; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013449:Sulfonamides / Q000627:therapeutic use*; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C501332:ABT-737; D001713:Biphenyl Compounds; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D009596:Nitrophenols; D010879:Piperazines; D019253:Proto-Oncogene Proteins c-bcl-2; D013449:Sulfonamides; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein