Poly(ADP-ribose) polymerase inhibition and its potential use in malignant melanoma

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Chemotherapy for metastatic malignant melanoma has disappointing response rates, with the majority of patients having resistant disease. One cause of such resistance is the repair of chemotherapy-induced potentially cytotoxic lesions by the DNA repair pathways. Inhibition of the DNA repair enzyme poly(ADP-ribose) polymerase-1 potentiates the cytotoxicity of temozolomide, and this combination has entered early clinical trials and may improve response rates and survival in metastatic melanoma. This review will discuss the rationale for this strategy for chemopotentiation and the early published results of the trials.

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