Greulich Heidi
Dana-Farber Cancer Institute, Boston, MA, USA.
Genes Cancer. 2010 Dec;1(12):1200-10. doi: 10.1177/1947601911407324.
Standard cytotoxic chemotherapy is effective for some cancers, but for many others, available treatments offer only a limited survival benefit. Lung adenocarcinoma is one such cancer, responsible for approximately half of lung cancer deaths each year. Development of targeted therapies is thought to hold the most promise for successfully treating this disease, but a targeted approach is dependent on understanding the genomic state of the tumor cells. Exon-directed sequencing of large numbers of lung adenocarcinoma tumor samples has provided an initial low-resolution image of the somatic mutation profile of these tumors. Such cancer sequencing studies have confirmed the high frequency of TP53 and KRAS mutations in lung adenocarcinoma, have found inactivating mutations in known tumor suppressor genes not previously associated with lung adenocarcinoma, and have identified oncogenic mutations of EGFR upon which the first targeted therapy for lung adenocarcinoma patients was based. Additional candidate oncogenes await functional validation. It is anticipated that upcoming whole-exome and whole-genome lung adenocarcinoma sequencing experiments will reveal a more detailed landscape of somatic mutations that can be exploited for therapeutic purposes.
标准的细胞毒性化疗对某些癌症有效，但对许多其他癌症而言，现有的治疗方法仅能带来有限的生存益处。肺腺癌就是这样一种癌症，每年约占肺癌死亡人数的一半。靶向治疗的发展被认为是成功治疗这种疾病最有希望的方法，但靶向治疗方法依赖于了解肿瘤细胞的基因组状态。对大量肺腺癌肿瘤样本进行外显子定向测序，已经初步提供了这些肿瘤体细胞突变图谱的低分辨率图像。此类癌症测序研究证实了肺腺癌中TP53和KRAS突变的高频率，发现了以前与肺腺癌无关的已知肿瘤抑制基因中的失活突变，并确定了首个针对肺腺癌患者的靶向治疗所基于的EGFR致癌突变。其他候选致癌基因有待功能验证。预计即将开展的全外显子组和全基因组肺腺癌测序实验将揭示更详细的体细胞突变图谱，可用于治疗目的。
