In vivo inhibition of c-MYC in the metastatic drug-resistant ovarian cancer cells down regulates the c-MYC-PD-L1-PAX8-p21 to achieve therapeutic efficacy

Metastatic, drug-resistant ovarian cancer is the deadliest form of gynecological cancer afflicting women globally, with > 49% relapse rate following initial diagnosis, surgery and treatment. High-grade serous ovarian cancer is the most diagnosed type of ovarian cancer. In the USA, 21,000 patients are diagnosed annually, with > 50% of patients succumbing to the disease due to metastasis and treatment resistance. The mainstay treatment for ovarian cancer is platinum-based chemotherapy, such as cisplatin or carboplatin and in combination with a taxane (paclitaxel/docetaxel). However, patients often become resistant to it, due to the pervasive oncogenic signal driving cancer drug resistance. One such oncogene is c-MYC. 30-60% of high-grade serous and drug-resistant (paclitaxel and carboplatin) ovarian cancer overexpress c-MYC, leading to progressive disease and mortality. Herein, it was shown that the novel c-MYC mRNA drug 3'UTRMYC1-18 achieved a dose-dependent titratable downregulation of the c-MYC mRNA with a half-maximal inhibitory concentration superior to the standard-of-care drugs, and with anti-cancer migration and viability properties. By using patient-derived xenograft (PDX) in-vivo, it was shown that the c-MYC mRNA drug significantly inhibited ovarian cancer through the downregulation of c-MYC, programmed death-ligand 1, paired box gene 8 and p21. This drug provides a novel therapy to target drug-resistant ovarian cancer cells.