The future of targeted kinase inhibitors in melanoma

被引:22
作者
Caksa, Signe [1 ]
Baqai, Usman [1 ]
Aplin, Andrew E. [1 ,2 ,3 ]
机构
[1] Thomas Jefferson Univ, Dept Canc Biol, Philadelphia, PA 19107 USA
[2] Thomas Jefferson Univ, Sidney Kimmel Canc Ctr, Philadelphia, PA 19107 USA
[3] Thomas Jefferson Univ, Sidney Kimmel Canc Ctr, 522 S 10 th St, Philadelphia, PA 19107 USA
关键词
Cancer; Melanoma; Targeted therapy; Kinase inhibitors; Immune checkpoint inhibitors; Combination therapy; MUTATED METASTATIC MELANOMA; DABRAFENIB PLUS TRAMETINIB; NRAS-MUTANT MELANOMA; MAPK PATHWAY INHIBITORS; T-CELL RECOGNITION; UVEAL MELANOMA; OPEN-LABEL; PHASE-II; ACQUIRED-RESISTANCE; MEK INHIBITION;
D O I
10.1016/j.pharmthera.2022.108200
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Melanoma is a cancer of the pigment-producing cells of the body and its incidence is rising. Targeted inhibitors that act against kinases in the MAPK pathway are approved for BRAF-mut ant metastatic cutaneous melanoma and increase patients' survival. Response to these therapies is limited by drug resistance and is less durable than with immune checkpoint inhibition. Conversely, rare melanoma subtypes have few therapeutic options for advanced disease and MAPK pathway targeting agents show minimal anti-tumor effects. Nevertheless, there is a future for targeted kinase inhibitors in melanoma: in new applications such as adjuvant or neoadjuvant therapy and in novel combinations with immunotherapies or other targeted therapies. Pre-clinical studies continue to identify tumor dependencies and their corresponding actionable drug targets, paving the way for rational targeted kinase inhibitor combinations as a personalized medicine approach for melanoma. (c) 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).
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页数:21
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