Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade-Reference-Cited by-同舟云学术

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

Published:2017-07-28 Issue:6349 Volume:357 Page:409-413
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Le Dung T.¹²³^ORCID,Durham Jennifer N.¹²³^ORCID,Smith Kellie N.¹³^ORCID,Wang Hao³,Bartlett Bjarne R.²⁴^ORCID,Aulakh Laveet K.²⁴,Lu Steve²⁴^ORCID,Kemberling Holly³^ORCID,Wilt Cara³^ORCID,Luber Brandon S.³,Wong Fay²⁴^ORCID,Azad Nilofer S.¹³,Rucki Agnieszka A.¹³,Laheru Dan³,Donehower Ross³,Zaheer Atif⁵^ORCID,Fisher George A.⁶,Crocenzi Todd S.⁷^ORCID,Lee James J.⁸^ORCID,Greten Tim F.⁹^ORCID,Duffy Austin G.⁹^ORCID,Ciombor Kristen K.¹⁰^ORCID,Eyring Aleksandra D.¹¹,Lam Bao H.¹¹,Joe Andrew¹¹,Kang S. Peter¹¹,Holdhoff Matthias³,Danilova Ludmila¹³^ORCID,Cope Leslie¹³^ORCID,Meyer Christian³^ORCID,Zhou Shibin¹³⁴^ORCID,Goldberg Richard M.¹²^ORCID,Armstrong Deborah K.³,Bever Katherine M.³^ORCID,Fader Amanda N.¹³,Taube Janis¹³,Housseau Franck¹³,Spetzler David¹⁴,Xiao Nianqing¹⁴^ORCID,Pardoll Drew M.¹³,Papadopoulos Nickolas³⁴,Kinzler Kenneth W.³⁴,Eshleman James R.¹⁵^ORCID,Vogelstein Bert¹³⁴^ORCID,Anders Robert A.¹³¹⁵,Diaz Luis A.¹²³^ORCID

Affiliation:

1. Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Baltimore, MD 21287, USA.

2. Swim Across America Laboratory at Johns Hopkins, Baltimore, MD 21287, USA.

3. Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287, USA.

4. Ludwig Center and Howard Hughes Medical Institute at Johns Hopkins, Baltimore, MD 21287, USA.

5. Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.

6. Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.

7. Providence Cancer Center at Providence Health & Services, Portland, OR 97213, USA.

8. Department of Medicine, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15232, USA.

9. Gastrointestinal Malignancies Section, Thoracic-GI Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.

10. Division of Medical Oncology, Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA.

11. Merck & Co. Inc., Kenilworth, NJ 07033, USA.

12. West Virginia University Cancer Institute, Morgantown, WV 26506, USA.

13. Department of Gynecology and Obstetrics, Johns Hopkins Medicine, Baltimore, MD 21287, USA.

14. Caris Life Sciences, Phoenix, AZ 85040, USA.

15. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.

Abstract

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

Funder

Commonwealth Fund

Lustgarten Foundation

Ludwig Institute for Cancer Research

Stand Up To Cancer

Bloomberg Kimmel Institute for Cancer Immunotherapy

Swim Across America

The Banyan Gate Foundation

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary