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辅助治疗的进展:预后和预测生物标志物的潜力

Advances in adjuvant therapy: potential for prognostic and predictive biomarkers.

作者信息

Davar Diwakar, Tarhini Ahmad A, Gogas Helen, Kirkwood John M

机构信息

Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.

出版信息

Methods Mol Biol. 2014;1102:45-69. doi: 10.1007/978-1-62703-727-3_4.

Abstract

Melanoma is the third most common skin cancer but accounts for the majority of skin cancer-related mortality. The rapidly rising incidence and younger age at diagnosis has made melanoma a leading cause of lost productive years of life and has increased the urgency of finding improved adjuvant therapy for melanoma. Interferon-α was approved for the adjuvant treatment of resected high-risk melanoma following studies that demonstrated improvements in relapse-free survival and overall survival that were commenced nearly 30 years ago. The clinical benefits associated with this agent have been consistently observed across multiple studies and meta-analyses in terms of relapse rate, and to a smaller and less-consistent degree, mortality. However, significant toxicity and lack of prognostic and/or predictive biomarkers that would allow greater risk-benefit ratio have limited the more widespread adoption of this modality.Recent success with targeted agents directed against components of the MAP-kinase pathway and checkpoint inhibitors have transformed the treatment landscape in metastatic disease. Current research efforts are centered around discovering predictive/prognostic biomarkers and exploring the options for more effective regimens, either singly or in combination.

摘要

黑色素瘤是第三常见的皮肤癌,但却是皮肤癌相关死亡的主要原因。其发病率迅速上升且诊断年龄趋于年轻化,这使得黑色素瘤成为导致生产性寿命损失的主要原因,并增加了寻找改善黑色素瘤辅助治疗方法的紧迫性。大约30年前开展的研究表明,干扰素-α可改善无复发生存期和总生存期,随后它被批准用于切除后的高危黑色素瘤的辅助治疗。多项研究和荟萃分析在复发率方面一致观察到了该药物的临床益处,而在死亡率方面,虽有观察到但程度较小且不太一致。然而,显著的毒性以及缺乏能够实现更高风险效益比的预后和/或预测生物标志物,限制了这种治疗方式的更广泛应用。针对丝裂原活化蛋白激酶(MAP)激酶途径成分的靶向药物和检查点抑制剂最近取得的成功改变了转移性疾病的治疗格局。目前的研究工作主要集中在发现预测性/预后性生物标志物以及探索更有效治疗方案的选择,无论是单一用药还是联合用药。

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