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

Abstract

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.

PRAME Updated: Diagnostic, Prognostic, and Therapeutic Role in Skin Cancer

“…Melanoma-associated antigen PRAME, or Preferentially expressed Antigen in Melanoma, has emerged as a promising target in cancer research, particularly in the context of melanoma [1].…”

“…Preferentially expressed Antigen in Melanoma (PRAME), also known as CT130 (cancer testis antigen 130), MAPE (melanoma antigen preferentially expressed in tumours), and OIP-4 (Opa-interacting protein 4) [1], belongs to the cancer/testis antigen (CTA) gene family [2] and encodes a membrane-bound protein recognised by T lymphocytes, which is a cancer-testis antigen that was first identified in 1997 in cutaneous melanoma by Ikeda et al [3]. PRAME is a member of a class of tumour-associated antigens.…”

Dark horse target Claudin18.2 opens new battlefield for pancreatic cancer

“…There are many antigens with dual roles in tumor microenvironment, for example, TGF-β, desmosomes, HMGB1 (a nuclear DNA-binding protein) and cancer testis antigens etc. ( 27 – 30 ). Claudin18 also has different effects in tumors, acting as a tumor suppressant in gastric and lung cancers, but playing a promoting role in other gastrointestinal tumors, such as pancreatic cancer, colorectal cancer, and esophageal cancer ( 31 ).…”

Expression of Immunotherapy Target PRAME in Cancer Correlates with Histone H3 Acetylation and Is Unrelated to Expression of Methylating (DMNT3A/3B) and Demethylating (TET1) Enzymes

“…PRAME is a transcriptional repressor of retinoic acid signaling and thereby regulates cellular growth, differentiation, and apoptosis [ 2 ]. Moreover, it has been implicated in the promotion of invasion, metastasis, epithelial-to-mesenchymal transition, and genomic instability in a number of cancers [ 3 , 4 , 5 , 6 , 7 ]. Notably, cytotoxic T lymphocytes have been shown to effectively target PRAME-expressing cancer cells [ 8 , 9 ].…”