Efficacy of PARP inhibitor therapy after targeted BRAF/MEK failure in advanced melanoma

IF 6.8 1区医学 Q1 ONCOLOGY NPJ Precision Oncology Pub Date : 2024-09-05 DOI:10.1038/s41698-024-00684-w

Jordan Phillipps, George Nassief, Renee Morecroft, Tolulope Adeyelu, Andrew Elliott, Farah Abdulla, Ari Vanderwalde, Soo Park, Omar Butt, Alice Zhou, George Ansstas

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Abstract

Modern advancements in targeted therapy and immunotherapy have significantly improved survival outcomes for advanced melanoma; however, there remains a need for novel approaches to overcome disease progression and treatment resistance. In recent years, PARPi therapy has shown great promise both as a single regimen and in combination with other therapeutics in melanoma. Here, we describe three unique cases of advanced BRAF V600 mutated melanoma that progressed on targeted BRAF/MEK agents that subsequently exhibited partial to near-complete responses to combinatory PARPi and BRAF/MEK inhibitors. This highlights both a potential synergy underlying this combinatory approach and its efficacy as a treatment option for patients with advanced melanoma refractory to targeted and/or immunotherapies. Prospective clinical trials are needed to explore this synergic effect in larger melanoma cohorts to investigate this combination for treating refractory advanced melanoma.

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晚期黑色素瘤 BRAF/MEK 靶向治疗失败后的 PARP 抑制剂疗效。

靶向治疗和免疫疗法的现代进展大大改善了晚期黑色素瘤患者的生存状况；然而，我们仍然需要新的方法来克服疾病进展和治疗耐药性。近年来，PARPi疗法无论是作为单一疗法还是与其他疗法联合用于黑色素瘤治疗，都显示出了巨大的前景。在这里，我们描述了三例独特的晚期 BRAF V600 突变黑色素瘤病例，这些病例在使用 BRAF/MEK 靶向药物治疗后取得了进展，随后对联合 PARPi 和 BRAF/MEK 抑制剂表现出部分或接近完全的反应。这凸显了这种联合疗法的潜在协同作用，以及它作为靶向和/或免疫疗法难治性晚期黑色素瘤患者治疗选择的有效性。需要进行前瞻性临床试验，在更大的黑色素瘤队列中探索这种协同作用，研究这种联合疗法治疗难治性晚期黑色素瘤的效果。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

NPJ Precision Oncology ONCOLOGY-

CiteScore

9.90

自引率

1.30%

发文量

审稿时长

18 weeks

期刊介绍： Online-only and open access, npj Precision Oncology is an international, peer-reviewed journal dedicated to showcasing cutting-edge scientific research in all facets of precision oncology, spanning from fundamental science to translational applications and clinical medicine.