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

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 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.

Disulfidptosis-associated LncRNAs index predicts prognosis and chemotherapy drugs sensitivity in cervical cancer

“…For instance, Dactolisib, a dual PI3K and mTORC1/2 inhibitor has shown potential benefits in CC treatment 45 . Erlotinib treatment sensitizes CSCs to paclitaxel treatment in vitro and in vivo 46 , Alpelisib demonstrates antitumor effects and enhances cisplatin efficacy through the PI3K/AKT pathway in PIK3CA mutant CC cells 47 . The expression of AL021707.6 as well as ZSCAN16-AS1 showed interesting correlation with the IC 50 of these drugs, indicating a new direction in the study of targeting drugs in CC.…”

Anti-cervical cancer mechanism of bioactive compounds from Alangium platanifolium based on the ‘compound-target-disease’ network

“…At present, molecular therapies targeting PI3K/AKT and MAPK signaling pathways are being extensively investigated for CC treatment. Preclinical studies have demonstrated that PI3K/AKT/mTOR pathway can be inhibited by Alpelisib, leading to the suppression of proliferation and migration of CC cells with PIK3CA mutations [ 57 ]. A novel polysaccharide of Rosa rugosa induced autophagy-mediated apoptosis in human CC cells primarily via the PI3K/AKT/mTOR pathway [ 58 ].…”

Multi‐omics data reveals novel impacts of human papillomavirus integration on the epigenomic and transcriptomic signatures of cervical tumorigenesis

“…Cervical cancer is one of the most common gynecological malignancies. It has both high morbidity and mortality, with an estimated 604 000 new cases and 342 000 deaths worldwide in 2020 1,2 . Human papilloma virus (HPV) is the major cause of cervical cancer, and 12 oncogenic types have been classified as group 1 carcinogens by the International Agency for Research on Cancer Monographs 3 .…”

“…It has both high morbidity and mortality, with an estimated 604 000 new cases and 342 000 deaths worldwide in 2020. 1,2 Human papilloma virus (HPV) is the major cause of cervical cancer, and 12 oncogenic types have been classified as group 1 carcinogens by the International Agency for Research on Cancer Monographs. 3 At present, hysterectomy and adjuvant chemo-and radiotherapy are the main treatments for early-and advanced-stage cervical cancer, respectively.…”