Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade

American Association for the Advancement of Science (AAAS) - Tập 357 Số 6349 - Trang 409-413 - 2017
Dung T. Le1,2,3, Jennifer N. Durham1,2,3, Kellie N. Smith1,2, Hao Wang2, Bjarne R. Bartlett4,3, Laveet K. Aulakh4,3, Steve Lu4,3, Holly Kemberling2, Cara Wilt2, Brandon Luber2, Fay Wong4,3, Nilofer S. Azad1,2, Agnieszka A. Rucki1,2, Dan Laheru2, Ross C. Donehower2, Atif Zaheer5, George A. Fisher6, Todd S. Crocenzi7, James J. Lee8, Tim F. Greten9, Austin G. Duffy9, Kristen K. Ciombor10, Aleksandra Eyring11, Bao Lam11, Andrew K. Joe11, Soonmo Peter Kang11, Matthias Holdhoff2, Ludmila Danilova1,2, Leslie Cope1,2, Christian F. Meyer2, Shibin Zhou1,4,2, Richard M. Goldberg12, Deborah K. Armstrong2, Katherine M. Bever2, Amanda N. Fader13, Janis M. Taube1,2, Franck Housseau1,2, David Spetzler14, Nianqing Xiao14, Drew M. Pardoll1,2, Nickolas Papadopoulos4,2, Kenneth W. Kinzler4,2, James R. Eshleman15, Bert Vogelstein1,4,2, Robert A. Anders1,15,2, Luis A. Díaz1,2,3
1Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Baltimore, MD 21287, USA.
2Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287, USA.
3Swim Across America Laboratory at Johns Hopkins, Baltimore, MD 21287, USA.
4Ludwig Center and Howard Hughes Medical Institute at Johns Hopkins, Baltimore, MD 21287, USA
5Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
6Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305 (USA)
7Providence Cancer Center at Providence Health & Services, Portland, OR 97213, USA.
8Department of Medicine, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15232, USA.
9Gastrointestinal Malignancies Section, Thoracic-GI Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
10Division of Medical Oncology, Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA.
11Merck & Co. Inc., Kenilworth, NJ 07033, USA.
12West Virginia University Cancer Institute, Morgantown, WV 26506, USA.
13Department of Gynecology and Obstetrics, Johns Hopkins Medicine, Baltimore, MD 21287, USA.
14Caris Life Sciences, Phoenix, AZ 85040, USA
15Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287 USA

Tóm tắt

Predicting responses to immunotherapy Colon cancers with loss-of-function mutations in the mismatch repair (MMR) pathway have favorable responses to PD-1 blockade immunotherapy. In a phase 2 clinical trial, Le et al. showed that treatment success is not just limited to colon cancer (see the Perspective by Goswami and Sharma). They found that a wide range of different cancer types with MMR deficiency also responded to PD-1 blockade. The trial included some patients with pancreatic cancer, which is one of the deadliest forms of cancer. The clinical trial is still ongoing, and around 20% of patients have so far achieved a complete response. MMR deficiency appears to be a biomarker for predicting successful treatment outcomes for several solid tumors and indicates a new therapeutic option for patients harboring MMR-deficient cancers. Science , this issue p. 409 ; see also p. 358

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