Oncogene
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Non-small-cell lung cancer (NSCLC) is a major global health problem and is the leading cause of cancer death worldwide. Current treatment involves nonspecific, nonselective cytotoxic chemotherapy, which results in only a modest increase in survival and causes significant toxicity to the patient. ⋯ The limitations in efficacy and safety associated with available treatments for NSCLC underscore the need for novel agents with improved efficacy and safety profiles. This review discusses the limitations of currently recommended therapies for patients with advanced NSCLC and discusses new agents in clinical development for this disease.
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Most patients with non-small-cell lung cancer (NSCLC) present with advanced disease. Current treatment paradigms are shifting from cytotoxic chemotherapies alone to single-agent and combination biological and targeted therapies. ⋯ Many techniques are available to assay for these biomarkers. In this review, we present the current weight of evidence for using these methods as biomarkers for anti-EGFR therapy in patients with NSCLC.
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The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs), gefitinib and erlotinib, are reversible competitive inhibitors of the tyrosine kinase domain of EGFR that bind to its adenosine-5' triphosphate-binding site. Somatic activating mutations of the EGFR gene, increased gene copy number and certain clinical and pathological features have been associated with dramatic tumor responses and favorable clinical outcomes with these agents in patients with non-small-cell lung cancer (NSCLC). The specific types of activating mutations that confer sensitivity to EGFR TKIs are present in the tyrosine kinase (TK) domain of the EGFR gene. ⋯ Most patients who initially respond to gefitinib and erlotinib eventually become resistant and experience progressive disease. The point mutation T790M accounts for about one half of these cases of acquired resistance. Various second-generation EGFR TKIs are currently being evaluated and may have the potential to overcome T790M-mediated resistance by virtue of their irreversible inhibition of the receptor TK domain.
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Review
Individualized therapy in non-small-cell lung cancer: future versus current clinical practice.
Despite advances in the management of non-small-cell lung cancer (NSCLC), including the introduction of targeted therapies such as epidermal growth factor receptor tyrosine kinase inhibitors, improvements in survival are marginal and the overall prognosis for patients remains poor. Tailoring therapy to the individual patient is a promising approach for selecting the most appropriate therapeutic regimens to maximize efficacy and minimize toxicity. ⋯ Genomic and proteomic studies provide a means for the molecular profiling of tumor tissue from patients with NSCLC, and allow tailoring of therapy whereby the most appropriate treatment is administered to each individual patient. Although there are still significant challenges to implementing genomic and proteomic testing in clinical practice, the rapid development of newer technologies provides hope for overcoming these barriers.
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Lung cancer is the leading cause of cancer deaths worldwide. Non-small-cell lung cancer (NSCLC) is the largest subgroup of the disease and accounts for approximately 80% of lung cancers. Most patients with NSCLC are diagnosed with locally advanced or metastatic disease. ⋯ Such a tailored approach would maximize both the therapeutic index and cost-effectiveness of treatments. In addition, several novel agents are under development, which may have the potential for overcoming acquired resistance to existing treatments. This supplement will review the current and emerging treatments for patients with advanced NSCLC and the molecular predictors of response that may facilitate the future clinical application of personalized medicine.