PARP1 in melanoma: Mechanistic insights and implications for basic and clinical research

Targeted therapies and immunotherapies have revolutionized the treatment of metastatic melanoma and have set a successful example for the treatment of other cancers. A similar breakthrough was achieved with the advent of PARP inhibitors (PARPi) in breast and ovarian cancer. Recent evidence highlights the critical role of PARP1 in melanoma initiation and progression. High PARP1 expression correlates with aggressive melanoma characteristics and poor patient outcomes. Preclinical and clinical data suggest that PARPi, alone or in combination, can effectively reduce melanoma cell viability and inhibit tumor growth. However, integrating PARPi with current treatment approaches and identifying patients who could benefit the most from such combinations remain underexplored areas of investigation. This review highlights the need for further basic and clinical research on PARP1 in melanoma, to better understand its role and to tackle major challenges in the field, such as resistance to targeted therapies and immune checkpoint inhibitors.