Preferentially Expressed Antigen in Melanoma Is a Multifaceted Cancer Testis Antigen with Diverse Roles as a Biomarker and Therapeutic Target

Preferentially expressed antigen in melanoma (PRAME) is a cancer testis antigen (CTA) that is selectively expressed in certain somatic tissues, predominantly in the testis, and is overexpressed in various cancers. PRAME family proteins are leucine-rich repeat proteins that are localized in the nucleus and cytoplasm, with multifaceted roles in immunity, during gametogenesis and in the overall reproduction process. It is a widely studied CTA and has been associated with the prognosis and therapeutic outcomes in patients with epithelial and non-epithelial tumors. PRAME has also been studied extensively as a therapeutic target. Moreover, it has been found to play a role in most of the well-known cancer hallmarks. Interestingly, the role of PRAME in tumorigenesis is paradoxical. Over the last decade, PRAME has garnered substantial interest as a target for immunotherapy. There are multiple clinical trials and pre-clinical studies targeting PRAME alone or in combination with other tumor antigens. This review article is an attempt to update our knowledge and understanding of the context-dependent oncogenic functions of PRAME in various carcinomas, and the current immunotherapeutic strategies, challenges, and perspectives on developing newer strategies to target PRAME for a better outcome.