The field of lung cancer molecular pathology is rapidly changing due to advances in our understanding of the molecular pathogenesis of tumors. In the past ten years, the identification of new molecular targets has provided unique opportunities to attack cancer with targeted therapies in a personalized manner. Recent advances in expanding the available non-small cell lung carcinoma (NSCLC) targeted therapies require the analysis of a broad panel of molecular abnormalities in tumor specimens, including gene mutations, amplifications, fusions and expression by applying different methodologies to frequently small tumor tissue (biopsy) and cell (cytology) samples. In addition, there is growing consensus that tumor tissue specimens must represent the setting of the disease to be treated, and increasingly, more tissue samples are being obtained for molecular testing of advanced, metastatic and chemo-refractory NSCLC tumors (e.g., MD Anderson BATTLE Lung Cancer Program). Currently available methodologies and technologies, including microarrays and next-generation sequencing, have variable applicability for the molecular and genomic analysis of these small specimens. Thus, the role of the pathologist is becoming increasingly important to adequately integrate routine histopathology assessments and molecular testing with clinical pathology for the most accurate tumor diagnosis and subsequent selection of the most appropriate therapy. In addition, applying high-throughput molecular methodologies currently used in studying established tumors to epithelial cell samples obtained from the airway of high-risk individuals and lung cancer patients is expanding our understanding of the early pathogenesis of lung cancer. Earlier studies have highlighted a field cancerization phenomenon in which histologically normal-appearing tissue adjacent to neoplastic and preneoplastic lesions display molecular abnormalities some of which are in common with those in the tumors. There is consensus that advances in the understanding of this field phenomenon will help to the development of biomarkers for early detection of and personalized chemoprevention of lung cancer.
Citation Format: Ignacio I. Wistuba. Promises and challenges of applying molecular profiles to lung cancer treatment and early diagnosis. [abstract]. In: Proceedings of the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer; 2014 Jan 6-9; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2014;20(2Suppl):Abstract nr IA11.