Lovly Christine M, Salama April K S, Salgia Ravi
From the Department of Medicine, Department of Cancer Biology, Vanderbilt Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN; Department of Internal Medicine, Duke University Medical Center, Durham, NC; Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, CA.
Am Soc Clin Oncol Educ Book. 2016;35:e585-93. doi: 10.1200/EDBK_158808.
The rapidly changing landscape of oncology has brought new light, and with it, new challenges to optimizing therapeutic strategies for patients. Although the concept of patient heterogeneity is well known to any practicing clinician, a more detailed understanding of the biologic changes that underscore the clinical picture is beginning to emerge. Thus, tumor heterogeneity has come to encompass more than just the clinical picture and can represent both intratumor and intertumor differences. Within the fields of thoracic oncology and melanoma, the discovery of key molecular drivers has resulted in landmark breakthroughs in therapy. However, the complexities of tumor genetics and the interaction within the environment continue to drive the search for better therapies. Ongoing challenges include the accurate and timely assessment of genetic changes as well as the development of resistance and the resultant compensatory mechanisms. Novel technologies, including commercially available next-generation sequencing, have allowed for a greater breadth and depth of information to be gained from a single pathologic specimen, and it is now being incorporated into routine clinical practice. Translational advances have subsequently provided valuable insight into mechanisms of resistance, with the development of novel treatment strategies. Future work will focus on novel diagnostic techniques and adaptive mechanisms that can ultimately drive the development of the next generation of cancer therapy.
肿瘤学领域迅速变化的形势带来了新的曙光，与此同时，也给优化患者治疗策略带来了新的挑战。尽管任何执业临床医生都熟知患者异质性的概念，但对构成临床症状基础的生物学变化的更详细理解正开始浮现。因此，肿瘤异质性已不仅仅涵盖临床症状，还可代表肿瘤内和肿瘤间的差异。在胸部肿瘤学和黑色素瘤领域，关键分子驱动因素的发现已带来了具有里程碑意义的治疗突破。然而，肿瘤遗传学的复杂性以及环境中的相互作用继续推动着对更好治疗方法的探索。持续存在的挑战包括对基因变化的准确及时评估以及耐药性的产生和由此产生的代偿机制。包括商用二代测序在内的新技术，使得能够从单个病理标本中获取更广泛和深入的信息，并且目前正被纳入常规临床实践。随后，转化医学的进展通过开发新的治疗策略，为耐药机制提供了有价值的见解。未来的工作将集中在新型诊断技术和适应性机制上，这些最终能够推动下一代癌症治疗的发展。
