Double PIK3CA mutations in cis increase oncogenicity and sensitivity to PI3Kα inhibitors-Reference-Cited by-同舟云学术

Double PIK3CA mutations in cis increase oncogenicity and sensitivity to PI3Kα inhibitors

Published:2019-11-08 Issue:6466 Volume:366 Page:714-723
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Vasan Neil¹²³^ORCID,Razavi Pedram¹²^ORCID,Johnson Jared L.³^ORCID,Shao Hong¹,Shah Hardik⁴^ORCID,Antoine Alesia⁴^ORCID,Ladewig Erik¹^ORCID,Gorelick Alexander¹⁵^ORCID,Lin Ting-Yu³^ORCID,Toska Eneda¹^ORCID,Xu Guotai¹^ORCID,Kazmi Abiha¹,Chang Matthew T.⁶,Taylor Barry S.¹⁵⁷^ORCID,Dickler Maura N.²⁸,Jhaveri Komal²,Chandarlapaty Sarat¹²^ORCID,Rabadan Raul⁹^ORCID,Reznik Ed⁵⁷^ORCID,Smith Melissa L.⁴¹⁰^ORCID,Sebra Robert⁴¹⁰¹¹,Schimmoller Frauke⁶,Wilson Timothy R.⁶,Friedman Lori S.¹²^ORCID,Cantley Lewis C.³^ORCID,Scaltriti Maurizio¹¹³^ORCID,Baselga José¹²^ORCID

Affiliation:

1. Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

2. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

3. Meyer Cancer Center, Department of Medicine, Weill Cornell Medical College, New York, NY, USA.

4. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

5. Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

6. Genentech, South San Francisco, CA, USA.

7. Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

8. Eli Lilly and Company, Indianapolis, IN, USA.

9. Departments of Systems Biology and Biomedical Informatics, Columbia University, New York, NY, USA.

10. Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

11. Sema4, Stamford, CT, USA.

12. ORIC Pharmaceuticals, South San Francisco, CA, USA.

13. Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Abstract

Seeing double can be a good thing Many human breast cancers harbor activating mutations in PIK3CA , the gene coding for the catalytic subunit of phosphoinositide 3-kinase (PI3K). Clinical trials are underway to evaluate the efficacy of PI3K inhibitors in cancer patients. Vasan et al. found unexpectedly that a subset of breast cancers harbor not one—but two— PIK3CA mutations, and the mutations occur on the same allele (see the Perspective by Toker). In model systems, the double mutations hyperactivate PI3K signaling and enhance tumor growth. Preliminary analysis of clinical trial data suggests that breast cancers with double mutations are more responsive to PI3K inhibitors than those with a single mutation. PIK3CA mutational status could help identify the breast cancer patients most likely to benefit from these drugs. Science , this issue p. 714 ; see also p. 685

Funder

National Science Foundation

National Institutes of Health

V Foundation for Cancer Research

Stand Up To Cancer

Conquer Cancer Foundation

National Cancer Institute

Society of MSK

Fund for Innovation in Cancer Informatics

Publisher

American Association for the Advancement of Science (AAAS)

Subject