1. Academic Validation
  2. Genomic analysis of cervical carcinoma identifies Alpelisib as a therapeutic option for PIK3CA-mutant cervical carcinoma via the PI3K/AKT pathway

Genomic analysis of cervical carcinoma identifies Alpelisib as a therapeutic option for PIK3CA-mutant cervical carcinoma via the PI3K/AKT pathway

  • J Med Virol. 2023 Mar 10. doi: 10.1002/jmv.28656.
Yei Wei 1 2 3 Shitong Lin 4 2 3 Wenhua Zhi 1 2 3 Tian Chu 1 2 3 Binghan Liu 4 2 3 Ting Peng 1 2 3 Maochun Xu 4 2 3 Wencheng Ding 5 2 3 Canhui Cao 1 2 3 6 Peng Wu 4 2 3
Affiliations

Affiliations

  • 1 Department of Gynecologic Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China.
  • 2 National Clinical Research Center for Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China.
  • 3 Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China.
  • 4 Department of Gynecology and Obstetrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China.
  • 5 Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
  • 6 Department of Gynecologic Oncology, Peking University Shenzhen Hospital, Shenzhen, Guangdong, 518083, China.
Abstract

Cervical carcinoma is a serious type of gynecological Cancer that can affect women of all ages. Cervical carcinoma presents challenges for precision medicine, as not all tumors have specific gene mutations or alterations that can be targeted with existing drugs. Nonetheless, there are some promising targets in cervical carcinoma. Herein, genomic mutation data from the Cancer Genome Atlas (TCGA) and Catalogue of Somatic Mutations in Cancer (COSMIC) were used to identify genomic targets for cervical carcinoma. PIK3CA was the most mutant gene among the promising targets, especially in cervical squamous cell carcinoma, and the mutated genes of cervical carcinoma were enriched in the RTK/PI3K/MAPK and Hippo pathways. In vitro, PIK3CA-mutant cervical Cancer cell lines showed higher sensitivity to Alpelisib than Cancer cells without the PIK3CA mutation and the normal cells (HCerEpic). Protein-protein networks and co-immunoprecipitation of PIK3CA revealed reduced interaction between p110α and ATR in PIK3CA-mutant cervical Cancer cells, which were sensitive to the combination of Alpelisib and cisplatin in vivo. Furthermore, Alpelisib significantly suppressed the proliferation and migration of PIK3CA-mutant cervical Cancer cells via inhibition of the Akt/mTOR pathway. Overall, Alpelisib showed antitumor effects and enhance cisplatin efficacy in PIK3CA-mutant cervical Cancer cells via PI3K/Akt pathways. Our study demonstrated the therapeutic potential of Alpelisib in PIK3CA-mutant cervical carcinoma, which provides insights into precision medicine in cervical carcinoma. This article is protected by copyright. All rights reserved.

Keywords

AKT/mTOR pathway; Alpelisib; Cervical carcinoma; Gene mutation; PIK3CA.

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