The Challenges and Prospects of p53-Based Therapies in Ovarian Cancer

It has been well established that mutations in the tumor suppressor gene, p53, occur readily in a vast majority of cancer tumors, including ovarian cancer. Typically diagnosed in stages three or four, ovarian cancer is the fifth leading cause of death in women, despite accounting for only 2.5% of all female malignancies. The overall 5-year survival rate for ovarian cancer is around 47%; however, this drops to an abysmal 29% for the most common type of ovarian cancer, high-grade serous ovarian carcinoma (HGSOC). HGSOC has upwards of 96% of cases expressing mutations in p53. Therefore, wild-type (WT) p53 and p53-based therapies have been explored as treatment options via a plethora of drug delivery vehicles including nanoparticles, viruses, polymers, and liposomes. However, previous p53 therapeutics have faced many challenges, which have resulted in their limited translational success to date. This review highlights a selection of these historical p53-targeted therapeutics for ovarian cancer, why they failed, and what the future could hold for a new generation of this class of therapies.

Automated summary

It is well known that p53 mutations are common in cancer tumors, including ovarian cancer. Ovarian cancer is often diagnosed at later stages and has a low survival rate, especially for high-grade serous ovarian carcinoma (HGSOC) which has a high prevalence of p53 mutations. Previous p53-based therapies for ovarian cancer have faced challenges and limited success. This review discusses the failures of historical p53-targeted therapeutics and the potential for new generation therapies.