From Medscape Hematology-Oncology Expert Column
Clinical and Molecular Biomarkers in Non-Small-Cell Lung Cancer
Posted 10/29/2008
Vincent Miller, MD; Trever Bivona, MD, PhDAuthor Information
Abstract
Recent advances in understanding the molecular basis of non-small-cell lung cancer (NSCLC) have heralded a revolution in personalized cancer medicine predicated on the detection and therapeutic exploitation of somatically mutated alleles of critical oncogenes such as the epidermal growth factor receptor (EGFR). This review summarizes an emerging paradigm for genome- and pathway-based molecular biomarkers whose goal is individualized clinical deployment of agents that modulate aberrant signal transduction pathways driving lung carcinogenesis. As such, these strategies hold promise for significantly improved survival in patients with NSCLC.
Introduction
NSCLC is the leading cause of cancer mortality in the United States and is histologically subdivided into adenocarcinoma, squamous-cell carcinoma, and large-cell carcinoma.[1] Adenocarcinoma, the most frequent subtype of NSCLC, is further subclassified as papillary, acinar, solid, or mixed subtype, with most tumors containing significant proportions of more than 1 subtype. The clinical, radiographic, and histopathologic heterogeneity of lung adenocarcinomas makes it imperative that molecular tests are developed that allow better classification of this disease and, in turn, therapies geared to individuals or subgroups of patients rather than continued empiricism.
For those diagnosed with advanced NSCLC, cytotoxic chemotherapy, when administered to chemotherapy-naive patients, extends median survival from 4 months without treatment to approximately 12 months.[2] The real but modest improvements in clinical outcome with cytotoxic chemotherapy provided, in part, the impetus for more detailed understanding of the molecular underpinnings of lung adenocarcinoma and the therapeutic development of targeted small-molecule inhibitors. Large-scale collaborative efforts such as the human genome project, cancer genome atlas sequencing project, and the lung cancer tumor sequencing projects have yielded insight into genomic alterations in tumors, thus identifying potential diagnostic and therapeutic targets[3]; among those targets identified is EGFR. The recognition that kinase inhibitors of EGFR are effective in patients harboring clinical and molecular predictive biomarkers has revolutionized the management of NSCLC. As such, the management of NSCLC exemplifies an emerging paradigm for personalized cancer medicine, relying upon the employment of biomarkers for tailored therapy.
Full article at http://www.medscape.com/viewarticle/582340_2
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