Moschos Stergios J, Pinnamaneni Ramya
Division of Hematology/Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Physicians Office Building, Suite 3116-CB#7305, 170 Manning Drive, Chapel Hill, NC 27599, USA.
Division of Hematology/Oncology, Department of Medicine, East Carolina University, 600 Moye Boulevard, Brody 3E127, Greenville, NC 27834, USA.
Surg Oncol Clin N Am. 2015 Apr;24(2):347-58. doi: 10.1016/j.soc.2014.12.011. Epub 2015 Jan 24.
Advances in the biology of melanoma have provided insights about chemoresistance and its genetic heterogeneity in parallel with advances in drug design, culminating in recent major treatment breakthroughs. Although clinical benefit of targeted therapies has been unquestionable, future advances are only possible if we understand the interplay between genetic aberrations and role of other crucial nongenetic changes yet to be identified by such projects as the Cancer Genome Atlas Project in Melanoma. Combination therapies, either among small molecule inhibitors themselves and/or with immunotherapies, may be the optimal strategy to prevent development of drug resistance inherently linked with such targeted therapies.
黑色素瘤生物学的进展为化疗耐药性及其基因异质性提供了见解,同时药物设计也取得了进展,最终促成了近期重大的治疗突破。尽管靶向治疗的临床益处毋庸置疑,但只有当我们理解基因畸变与其他关键非基因变化(尚未被黑色素瘤癌症基因组图谱项目等项目识别)之间的相互作用时,未来的进展才有可能实现。小分子抑制剂之间和/或与免疫疗法的联合疗法,可能是预防与此类靶向治疗固有相关的耐药性发展的最佳策略。