Division of Hematology/Oncology, Department of Internal Medicine, University of Pennsylvania, 3400 Spruce Street, 16 Penn Tower, Philadelphia, PA 19104, USA.
Nat Rev Clin Oncol. 2012 Sep;9(9):520-8. doi: 10.1038/nrclinonc.2012.123. Epub 2012 Jul 24.
Identification of germline mutations associated with significant cancer susceptibility has the potential to change all aspects of an individual's care, from screening to cancer treatment. For example, women with germline mutations in BRCA1 and BRCA2 have markedly elevated risks of breast and ovarian cancer and the identification of these germline mutations has led to specific screening and prevention strategies. More recently, advances in the understanding of the biological function of BRCA1 and BRCA2 have led to clinical trials testing targeted therapies in this population, particularly poly(ADP-ribose) polymerase (PARP) inhibitors. Unfortunately, the development of PARP inhibitors has not been as rapid as anticipated and has been more challenging than expected. Somatic mutations identified in many cancer types have allowed the development of therapeutics that target these mutated genes, and many of these agents obtained rapid regulatory approval and are currently in widespread clinical practice. Diagnostic testing has a central role in targeted cancer therapeutics for both somatic and germline mutations. Although the era of molecular medicine and targeted therapies has led to significant changes in the practice of oncology, new challenges continue to arise.
鉴定与显著癌症易感性相关的种系突变有可能改变个体护理的各个方面，从筛查到癌症治疗。例如，BRCA1 和 BRCA2 种系突变的女性乳腺癌和卵巢癌的风险明显升高，这些种系突变的鉴定导致了特定的筛查和预防策略。最近，对 BRCA1 和 BRCA2 生物学功能的理解的进展导致了在该人群中测试靶向治疗的临床试验，特别是聚（ADP-核糖）聚合酶（PARP）抑制剂。不幸的是，PARP 抑制剂的开发并不像预期的那样迅速，并且比预期的更具挑战性。在许多癌症类型中鉴定的体细胞突变允许开发针对这些突变基因的治疗药物，其中许多药物获得了快速的监管批准，目前正在广泛的临床实践中使用。诊断测试在针对体细胞和种系突变的靶向癌症治疗中起着核心作用。尽管分子医学和靶向治疗的时代导致了肿瘤学实践的重大变化，但新的挑战仍在不断出现。
