Therapeutic potential of p53 reactivation in cervical cancer

• Published in: Critical reviews in oncology/hematology Vol. 157; p. 103182
• Main Authors: Zhao, Xiangxuan, Sun, Wei, Ren, Ying, Lu, Zaiming
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.01.2021
• Subjects: Apoptosis - genetics; Cell Line, Tumor; Cervical cancer; Female; Humans; Neoplasm Recurrence, Local; p53; Prognosis; Proto-Oncogene Proteins c-mdm2 - genetics; Signaling pathway; Targeted therapy; Tumor Suppressor Protein p53 - genetics; Uterine Cervical Neoplasms - drug therapy; Uterine Cervical Neoplasms - genetics; Prognosis; TIPE1; Targeted therapy; JNK; UCRs; AdCMV; IKKβ; ncRNAs; TSC-22; p53; CAV-1; MTA1; SNP; Signaling pathway; MSI-2/Mushshi-2; PLNM; CC; AC; LOH; ICC; CIN; DOX; OSR; CDK9; PFSR; T-UCRs; SCC; ALA; ROS; SIL; MDM2; MVD; DHA; HR-HPV; Cervical cancer; TAF1
• ISSN: 1040-8428; 1879-0461
• DOI: 10.1016/j.critrevonc.2020.103182

[Display omitted] •Dysfunction of p53 has been observed as a key contributing factor in cervical cancer.•Restoration of p53 activity can exert anti-tumor effects in cervical cancer cells.•Reactivation of p53 seems appealing as a therapeutic strategy in cervical cancer. Cervical cancer (CC) is one of most common malignancies affecting women worldwide. To date, surgical resection is the only effective radical remedy for CC at its early stages, while the prognosis of metastatic or recurrent CC is very poor. Dysfunction of the tumor suppressor p53 due to aberrant expression, post-translational modification, mutations, SNPs, and LOH as well as sequestration by viral antigens and MDM2/HDM2-mediated degradation is closely associated with the therapeutic insensitivity and relapse of many malignancies, including CC. Accumulating studies have demonstrated that restoration of p53 activity can induce cell cycle arrest and apoptosis, eliminate radio- and chemotherapy resistance, and inhibit tumor growth in CC cells. Therefore, activation of wild-type p53 as well as restoration of p53 function seems appealing as a therapeutic strategy. In this review, we focus on the potential roles of p53 reactivation in CC treatment and their underlying molecular mechanisms towards the development of novel therapies.