Agarwal Rishi, Liebe Sarah, Turski Michelle L, Vidwans Smruti J, Janku Filip, Garrido-Laguna Ignacio, Munoz Javier, Schwab Richard, Rodon Jordi, Kurzrock Razelle, Subbiah Vivek
Department of Medicine Division of Hematology/Oncology, University of Cincinnati, Cincinnati, OH 45267, USA.
UT Health, University of Texas - Houston, Houston, TX 77030, USA.
Discov Med. 2014 Dec;18(101):331-9.
Cancer genetics has rapidly evolved in the last two decades. Understanding and exploring the several genetic pathways in the cancer cell is the foundation of targeted therapy. Several genomic aberrations have been identified and their role in carcinogenesis is being explored. In contrast to most cancers where these mutations are acquired, patients with hereditary cancer syndromes have inherited genomic aberrations. The understanding of the molecular pathobiology in hereditary cancer syndromes has advanced dramatically. In addition, many molecularly targeted therapies have been developed that could have potential roles in the treatment of patients with hereditary cancer syndromes. In this review, we outline the presentation, molecular biology, and possible targeted therapies for two of the most widely recognized hereditary cancer syndromes -- hereditary breast and ovarian cancer syndrome and hereditary non-polyposis colorectal cancer syndrome (Lynch syndrome). We will also discuss other syndromes such as familial adenomatous polyposis and Li-Fraumeni syndrome (TP53).
癌症遗传学在过去二十年中迅速发展。了解和探索癌细胞中的多种遗传途径是靶向治疗的基础。已经鉴定出几种基因组畸变，并且正在探索它们在致癌作用中的作用。与大多数癌症中这些突变是后天获得的情况不同，遗传性癌症综合征患者具有遗传的基因组畸变。对遗传性癌症综合征分子病理生物学的理解有了巨大进展。此外，已经开发出许多分子靶向疗法，这些疗法可能在遗传性癌症综合征患者的治疗中发挥潜在作用。在本综述中，我们概述了两种最广为人知的遗传性癌症综合征——遗传性乳腺癌和卵巢癌综合征以及遗传性非息肉病性结直肠癌综合征（林奇综合征）的临床表现、分子生物学和可能的靶向治疗方法。我们还将讨论其他综合征，如家族性腺瘤性息肉病和李-弗劳梅尼综合征（TP53）。
