The Genomics of Lung Adenocarcinoma: Opportunities for Targeted Therapies

Abstract

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.