Lung cancer is the leading cause of cancer related mortality in the United States.  Classically, treatment decisions have been empiric and based upon histology of the tumor. Platinum based chemotherapy remains the cornerstone of treatment. However, survival rates remain low. Novel therapies and treatment strategies are needed.

Lung cancer is comprised of two main histologic subtypes: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Over the past decade, it has become evident that subsets of NSCLC can be further defined at the molecular level by recurrent 'driver' mutations that occur in multiple oncogenes, including AKT1, ALK, BRAF, EGFR, HER2, KRAS, MEK1, MET, NRAS, PIK3CA, RET, and ROS1.Another altered kinase gene involves MET. 'Driver' mutations lead to constitutive activation of mutant signaling proteins that induce and sustain tumorigenesis. These mutations are rarely found concurrently in the same tumor. Mutations can be found in all NSCLC histologies (including adenocarcinoma, squamous cell carcinoma (SCC), and large cell carcinoma) and in current, former, and never smokers (defined by individuals who smoked less than 100 cigarettes in a lifetime). Never smokers with adenocarcinoma have the highest incidence of EGFR, HER2, ALK, RET, and ROS1 mutations. Importantly, targeted small molecule inhibitors are currently available or being developed for specific molecularly defined subsets of lung cancer patients.

Historically, efforts at characterizing the molecular underpinnings of SCC of the lung have lagged behind those of adenocarcinoma of the lung. Many of the 'driver' mutations found in lung adenocarcinoma are only rarely found in lung SCC. Moreover, newer agents, such as bevacizumab (Avastin) and pemetrexed (Alimta) are not approved for or exhibit diminished efficacy in SCC (Sandler et al. 2006; Scagliotti et al. 2008). Thus, patients with metastatic SCC have fewer treatment options than those with non-squamous NSCLC. Despite these caveats, however, 'driver' mutations that may be linked to outcomes with targeted therapies in SCC are emerging. Altered genes include FGFR1 and DDR2 as well as PIK3CA.

* - SCLC Panel