Work

PIK3CA C-terminal frameshift mutations are novel oncogenic events that sensitize tumors to PI3K-α inhibition

Year: 2020

Type: article

Abstract: Significance While PIK3CA hotspot mutations frequently occur in solid cancers and in some contexts are therapeutically actionable, numerous other PIK3CA genomic alterations have been observed but remain uncharacterized. The authors identify C-terminal PIK3CA frameshift mutations as oncogenic driver events dependent on p85 binding in breast cancer and other cancers. Breast cell lines and tumors expressing PIK3CA frameshift mutations are sensitive to PI3K inhibition via alpelisib treatment. Patients with tumors characterized by these mutations may derive clinical benefit from p110α-selective inhibition.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.2000060117

Authors: Jennifer M. Spangle, Thanh Von, Dean C. Pavlick, Arina Khotimsky, Jean J. Zhao, Thomas M. Roberts

Institutions: Harvard University, Dana-Farber Cancer Institute, Foundation Medicine (United States)

Language: English

Topic: PI3K/AKT/mTOR signaling in cancer

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Institutes of Health, Stand Up To Cancer, National Cancer Institute