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

Abstract

AbstractCervical 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 and Catalogue of Somatic Mutations in Cancer 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.