Investigating the Efficacy and Mechanism of Action of ONC201 in Cervical Carcinoma Cells

Abstract

Cervical cancer ranks as the fourth most common cancer in women worldwide. In the US, there are 2.50,000 women who have this cancer, 12,820 new cases, and 4,210 fatalities per year. One kind of cancer that develops in the cells of the cervix the lower portion of the uterus that joins the vagina is called cervical cancer. In almost all cases, chronic high-risk (human papillomavirus) HPV infections cause cervical carcinogenesis. About 70% of cervical cancers are linked to the high-risk HPV subtypes HPV16 and HPV18, out of the 15 carcinogenic HPV subtypes that have been identified, including HPV 6, 11, 31, 33, 45, 52, 58, and others. newlineCervical cancer cases have considerably decreased as a result of preventive treatment with the HPV vaccinations Cervarix and Gardasil-9. Additional cervical cancer treatment options include surgery (total hysterectomy and radical hysterectomy), chemotherapy with a combination of Gemcitabine and Cisplatin or Cisplatin and 5 Fluorouracil, and occasionally, a targeted medication called Bevacizumab (Avastin) is used in conjunction with chemotherapy. For cervical cancer in the IB IIA stage, radiotherapy is recommended; however, it may be used in conjunction with chemotherapy if the cancer has returned. newlineA new class of anti-cancer drugs termed imipridones, of which ONC201 is a founding member, is presently undergoing Phase II clinical studies in a number of advanced malignancies. Preclinical research has shown that ONC201 has anti-proliferative and pro-apoptotic actions against a variety of tumor cells but not normal cells since it was discovered to be a p53-independent inducer of TRAIL gene transcription. The way that ONC201 works is by activating the integrated stress response without PERK, which causes tumor overexpression of DR5 and dual Akt/ERK inactivation. Foxo3a activation then causes the death ligand TRAIL to be upregulated...