Dong-Joon Min1, Siping He1, Jeffrey E Green2. 1. Transgenic Oncogenesis and Genomics Section, Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD, U.S.A. 2. Transgenic Oncogenesis and Genomics Section, Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD, U.S.A. jegreen@nih.gov.
Abstract
BACKGROUND: Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer currently lacking targeted therapies. Our previous work demonstrated a therapeutic synergism with gemcitabine (GEM) and the CHK1 inhibitor (AZD7762) combination treatment in a TNBC cell line. We hypothesized that the response to this combination therapy would differ among heterogeneous TNBC patients and that addition of a SMAC mimetic (TL32711) could improve efficacy. MATERIALS AND METHODS: Therapeutic responses to GEM, GEM/AZD7762, and GEM/AZD7762/TL32711 combinations were investigated by XTT assays and western blotting of cell cycle and apoptosis-related proteins in ten TNBC cell lines. RESULTS: TNBC cell lines harboring low levels of endogenous CHK1, cIAP1 and cIAP2 were responsive to GEM alone, whereas cell lines demonstrating a minimal increase in phospho-S345 CHK1 after treatment were responsive to GEM/AZD7762 or GEM/AZD7762/TL32711 combination. CONCLUSION: The response of TNBC cells to particular therapies varies and will require development of predictive biomarkers. Copyright
BACKGROUND: Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer currently lacking targeted therapies. Our previous work demonstrated a therapeutic synergism with gemcitabine (GEM) and the CHK1 inhibitor (AZD7762) combination treatment in a TNBC cell line. We hypothesized that the response to this combination therapy would differ among heterogeneous TNBC patients and that addition of a SMAC mimetic (TL32711) could improve efficacy. MATERIALS AND METHODS: Therapeutic responses to GEM, GEM/AZD7762, and GEM/AZD7762/TL32711 combinations were investigated by XTT assays and western blotting of cell cycle and apoptosis-related proteins in ten TNBC cell lines. RESULTS: TNBC cell lines harboring low levels of endogenous CHK1, cIAP1 and cIAP2 were responsive to GEM alone, whereas cell lines demonstrating a minimal increase in phospho-S345 CHK1 after treatment were responsive to GEM/AZD7762 or GEM/AZD7762/TL32711 combination. CONCLUSION: The response of TNBC cells to particular therapies varies and will require development of predictive biomarkers. Copyright
Authors: Svetlana Grabauskiene; Edward J Bergeron; Guoan Chen; Andrew C Chang; Jules Lin; Dafydd G Thomas; Thomas J Giordano; David G Beer; Meredith A Morgan; Rishindra M Reddy Journal: Lung Cancer Date: 2013-09-23 Impact factor: 5.705
Authors: Sohrab P Shah; Andrew Roth; Rodrigo Goya; Arusha Oloumi; Gavin Ha; Yongjun Zhao; Gulisa Turashvili; Jiarui Ding; Kane Tse; Gholamreza Haffari; Ali Bashashati; Leah M Prentice; Jaswinder Khattra; Angela Burleigh; Damian Yap; Virginie Bernard; Andrew McPherson; Karey Shumansky; Anamaria Crisan; Ryan Giuliany; Alireza Heravi-Moussavi; Jamie Rosner; Daniel Lai; Inanc Birol; Richard Varhol; Angela Tam; Noreen Dhalla; Thomas Zeng; Kevin Ma; Simon K Chan; Malachi Griffith; Annie Moradian; S-W Grace Cheng; Gregg B Morin; Peter Watson; Karen Gelmon; Stephen Chia; Suet-Feung Chin; Christina Curtis; Oscar M Rueda; Paul D Pharoah; Sambasivarao Damaraju; John Mackey; Kelly Hoon; Timothy Harkins; Vasisht Tadigotla; Mahvash Sigaroudinia; Philippe Gascard; Thea Tlsty; Joseph F Costello; Irmtraud M Meyer; Connie J Eaves; Wyeth W Wasserman; Steven Jones; David Huntsman; Martin Hirst; Carlos Caldas; Marco A Marra; Samuel Aparicio Journal: Nature Date: 2012-04-04 Impact factor: 49.962
Authors: Darlene Barnard; H Bruce Diaz; Teresa Burke; Gregory Donoho; Richard Beckmann; Bonita Jones; David Barda; Constance King; Mark Marshall Journal: Invest New Drugs Date: 2015-11-27 Impact factor: 3.850
Authors: C Maas; J M Tromp; J van Laar; R Thijssen; J A Elias; A Malara; A Krippner-Heidenreich; J Silke; M Hj van Oers; E Eldering Journal: Cell Death Dis Date: 2013-08-29 Impact factor: 8.469