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Lung cancer is the leading cause of cancer-related deaths in United States, accounting for more than one-fourth of the deaths annually. Although comparatively rare and relatively less studied, genetic abnormalities other than epidermal growth factor receptor (EGFR) mutations, anaplastic lymphoma kinase (ALK) rearrangements, and Kirsten rat sarcoma (KRAS) mutations account for significant proportion of the driver mutations identified thus far. The targeted agents against B-rapidly accelerated fibrosarcoma (BRAF) V600E mutation, MNNG-HOS transforming gene (MET) pathway, ROS1 rearrangement, rearranged during transfection (RET) rearrangement, and HER2 pathways offer promising therapeutic options. Recruiting patients with these rarer mutations to well-designed, large multicenter trials to further validate the use of targeted agents remains a challenge. The clinical data and ongoing trials with these agents are reviewed in this article.

Laboratory data suggest an association between statins and risk of brain metastasis (BM) in patients diagnosed with lung cancer. Our retrospective cohort included 252 patients diagnosed with lung cancer and 55 (22%) patients subsequently developed BM. The risk of BM was significantly higher in younger patients (p < .0007). The multivariable Cox model did not show a significant association between statin use and BM from lung cancer (Hazard-Ratio (HR) = 1.20, 95% confidence interval (CI): 0.68-2.13). Future studies should focus on late stage NSCLC and examine the incidence of BM among statin users at the time of death.

The incidence of lung cancer in females is increasing, in contrast to that seen in males. In addition, the proportion of lung cancer cases in women attributable to smoking is approximately half of that seen in males. Female sex hormones, especially estrogen, may play a key role in this. Estrogen receptors ERalpha and ERbeta have been detected on lung cancer cells and there is new evidence suggesting that hormone-replacement therapy may increase both the incidence of, and mortality from, lung cancer in women. Laboratory evidence lends credence to the carcinogenic effects of estrogens in lung cancer. This article summarizes the current evidence on their role in lung cancer.

Epidermal growth factor is a 170-kd protein that binds to a specific tyrosine kinase receptor, epidermal growth factor receptor (EGFR), on the cell surface. EGFR function is dysregulated in various malignancies including nonsmall cell lung cancer (NSCLC) leading to activation of several signal transduction pathways including K-RAS, PIK3, and STAT3 and STAT5, that promote cell cycle progression, proliferation, invasion, angiogenesis, and inhibit apoptosis. EGFR overexpression is seen in a majority of cases of NSCLC, but its prognostic role is controversial. EGFR inhibitors currently undergoing clinical trials in NSCLC include monoclonal antibodies or small molecule tyrosine kinase inhibitors. The only EGFR inhibitor currently approved for the treatment of NSCLC is erlotinib, a small molecule tyrosine kinase inhibitor. Although women, nonsmokers, patients with adenocarcinoma and patients with Asian ethnicity seem to have better outcomes with erlotinib, the factors predictive for response to these agents are currently the focus of investigation.

Cyclins and cyclin-dependent kinases (CDK) form a key part of the regulatory proteins that govern the cell cycle. Aberrancy in their function can lead to uncontrolled growth and proliferation of the cells which forms the basis of many human diseases, especially cancers. Seliciclib (CYC202, R-roscovitine) is a second-generation CDK inhibitor that competes for ATP binding sites on these kinases, reducing tumor growth and inducing cell death. It is a direct inhibitor of cyclin E/CDK2 and also has inhibitory effects on cyclin H/CDK7 and cyclin T/CDK9. Seliciclib leads to growth arrest and apoptosis of cell lines through activation of the p53 gene, inhibition of RNA processing and blockage of the RNA polymerase II-dependent transcription, and reduction of anti-apoptotic proteins. Seliciclib has good oral bioavailability, although its absorption is slowed by food. It is distributed rapidly to the body tissues and metabolized rapidly to a carboxylated derivative that is excreted by the kidneys. The major adverse effects of seliciclib are electrolyte disturbances (hypokalemia, hyponatremia), gastrointestinal side effects (nausea, emesis, anorexia), fatigue, transient hyperglycemia, elevation of liver enzymes and reversible elevation of serum creatinine. At present, it is in Phase II trials for non-small cell lung cancer and nasopharyngeal carcinoma.

Complete resection is mandatory in order to achieve a cure in patients with early-stage non-small cell lung cancer (NSCLC). However, despite complete resection, a substantial proportion of patients have disease recurrence, with distant metastases being the primary sites of failure. Recent trials have conclusively demonstrated the benefit of platinum-based adjuvant therapy in patients with resected stage IB and II NSCLC. The role of adjuvant chemotherapy in resected stage III NSCLC is less clear, with trials showing conflicting results. The role of targeted agents in this setting is being investigated. Gene expression profiling studies should help direct chemotherapy to those who would actually benefit from it, thereby saving others from unnecessary toxicity.

The epidermal growth factor receptor (EGFR) plays an important role in the carcinogenesis of many human malignancies and is therefore an attractive target against which anticancer therapy may be effective. At present, there are two ways in which this may be achieved clinically: antibodies against EGFR and inhibitors of the EGFR tyrosine kinase. This review describes presently approved agents cetuximab (monoclonal EGFR antibody), gefitinib and erlotinib (EGFR tyrosine kinase inhibitors) in detail. Efficacy data for these agents in various human malignancies is presented. Various other agents that are in the early stages of development at present have also been mentioned.

Body cavity-based lymphomas are fluid-based lymphomas that are not associated with a tumor mass or adenopathy which could explain the origin of the lymphomatous effusion. A distinct lymphoma that grows in the body cavity as a lymphomatous effusion in the absence of a tumor mass has been identified as a primary effusion lymphoma. This almost exclusively occurs in patients with acquired immunodeficiency syndrome (AIDS), who invariably have a history of Kaposi sarcoma. We report a rare case of a recurrent pleural effusion in an immunocompetent patient. There was no evidence of lymphadenopathy or an associated mass on computerized tomography of the chest, abdomen and pelvis. Serology for HIV, HHS-8, EBV and HTLV-1 were negative. Cytologic examination of the pleural fluid showed an elevated white cell count with 97% lymphocytes, mostly with T-cell markers. Bone marrow aspirate and biopsy were negative and bronchoscopy was unrevealing. Pleural biopsy was significant for >70% T-lymphocytes and some large atypical cells. Which had CD19, CD20 and weak bcl-2 positivity. Kappa and lambda light chains did not show distinct clonality. A preliminary diagnosis of T-cell rich B-cell lymphoma (TCRBCL) of the pleural cavity was made. The diagnosis was confirmed with DNA studies done on the pleural biopsy specimen using PCR and southern blot. Dual rearrangement of Ig heavy chain region and TCR-beta genes were identified. The patient responded to combination chemotherapy with cyclophosphamide, adriamycin, vincristine and prednisone. Our case is the first known case of pleural cavity-based TCRBCL and illustrates the role of gene rearrangement studies in such patients.