KRAS mutations predict response to EGFR inhibitors
ABSTRACT Five antiepidermal growth factor receptor therapies have been approved for the treatment of solid tumors. However, response rates are relatively low. Several biomarkers that enrich for patients with tumors most likely to respond to these therapeutic agents have been identified. Mutations in the intermediate signal transduction pathway member KRAS also selects patients with tumors depending on signaling through this pathway. However, because KRAS acts downstream of the EGF receptor, somatic changes in this gene can be used as a marker to exclude patients unlikely to benefit from anti-EGFR therapy. Recent clinical data have provided substantial evidence that KRAS mutational status should be utilized as a diagnostic marker for predicting that response to anti-EGFR therapies in colorectal and non-small cell lung cancer.
SourceAvailable from: Eftychia Oikonomou[Show abstract] [Hide abstract]
ABSTRACT: As the increased knowledge of tumour heterogeneity and genetic alterations progresses, it exemplifies the need for further personalized medicine in modern cancer management. Here, the similarities but also the differential effects of RAS and BRAF oncogenic signalling are examined and further implications in personalized cancer diagnosis and therapy are discussed. Redundant mechanisms mediated by the two oncogenes as well as differential regulation of signalling pathways and gene expression by RAS as compared to BRAF are addressed. The implications of RAS vs BRAF differential functions, in relevant tumour types including colorectal cancer, melanoma, lung cancer are discussed. Current therapeutic findings and future viewpoints concerning the exploitation of RAS-BRAF-pathway alterations for the development of novel therapeutics and efficient rational combinations, as well as companion tests for relevant markers of response will be evaluated. The concept that drug-resistant cells may also display drug dependency, such that altered dosing may prevent the emergence of lethal drug resistance posed a major therapy hindrance.Oncotarget 10/2014; · 6.63 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Lung cancer remains the most lethal malignancy in the world. Despite improvements in surgical treatment, systemic therapy, and radiotherapy, the 5-year survival rate for all patients diagnosed with lung cancer remains between 15 and 20%. Newer therapeutic strategies rely on specific molecular alterations, or biomarkers, that provide opportunities for a personalized approach to specific patient populations. Classification of lung cancer is becoming increasingly focused on these biomarkers, which renders the term "non-small cell lung" cancer less clinically useful. Non-small cell lung cancer is now recognized as a complex malignancy and its molecular and genomic diversity allows for patient-centered treatment options. Here, we review advances in targeted treatment of lung adenocarcinoma with respect to five clinically relevant biomarkers - EGFR, ALK, MET, ROS-1, and KRAS.Frontiers in Oncology 08/2014; 4:204. DOI:10.3389/fonc.2014.00204
[Show abstract] [Hide abstract]
ABSTRACT: Lung carcinoma is subdivided into small cell carcinoma and non-small cell carcinoma (NSCLC). NSCLC is heterogeneous group of carcinomas and accounts for 70–80% of lung cancer. NSCLC is further divided into adenocarcinoma, squamous cell carcinoma, and large cell carcinoma.Activating somatic mutations of the tyrosine kinase domain of epidermal growth factor receptor (EGFR) have recently been characterized in a subset of patients with non-small cell lung cancer (NSCLC). These mutations involve exons 18, 19, 20 and 21. Patients harboring these mutations in their tumors show good response to EGFR tyrosine kinase inhibitors (EGFR-TKIs). The aim of this manuscript is to provide an overview of EGFR mutations in NSCLC as well as to briefly discuss sample requirements and testing guidelines for EGFR mutation.Journal of Infection and Public Health 12/2012; 5:S31-S34. DOI:10.1016/j.jiph.2012.09.008