Abstract
Non-small-cell lung cancer (NSCLC) is a heterogeneous disease due to the presence of different clinically relevant molecular subtypes. Until today, several biological events have been identified in lung adenocarcinoma, including epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) translocations, offering new hopes to patients with metastatic disease. Unfortunately, in approximately 50% of adenocarcinoma and for those harbouring K-RAS mutations, the most frequent mutation in Caucasian lung adenocarcinoma, so far no specific drug demonstrated efficacy. The rat sarcoma (RAS) genes, including H-RAS, K-RAS, and N-RAS, encode a family of proteins regulating cell growth, differentiation, and apoptosis. K-RAS mutations are present in 20–30% of NSCLC and occur most commonly, but not exclusively, in adenocarcinoma histology and life-long smokers. Although in colorectal cancer patients K-RAS mutations represent a validated negative predictive biomarker for treatment with anti-EGFR monoclonal antibodies, their role in selecting specific treatment for NSCLC patients remains undefined. Aim of the present paper is to critically analyze the prognostic and predictive value of K-RAS mutations in NSCLC.
Highlights
In 2011 non-small-cell lung cancer (NSCLC) remains the principal cause of cancer-related death worldwide, accounting for more than one million deaths per year [1]
Six phase III randomized trials demonstrated that patients harboring activating Epidermal growth factor receptor (EGFR) mutations benefit more from EGFR-TKIs than from standard platinum-based chemotherapy at least in terms of response rate (RR), progression-free survival (PFS), toxicity profile and quality of life [7,8,9,10,11,12]
These results demonstrate that, unlike colorectal cancer case, the negative predictive value of K-rat sarcoma (RAS) mutations in NSCLC remains unclear
Summary
In 2011 non-small-cell lung cancer (NSCLC) remains the principal cause of cancer-related death worldwide, accounting for more than one million deaths per year [1]. In NSCLC a number of driving mutations have been identified, including Epidermal growth factor receptor (EGFR) mutations, KRAS mutations, HER2 mutations and EML4-ALK translocations. Since their identification in 2004, activating EGFR gene mutations have emerged as the most relevant predictor of response to a class of compounds, the EGFR tyrosine kinase inhibitors (EGFRTKIs) gefitinib and erlotinib. Six phase III randomized trials demonstrated that patients harboring activating EGFR mutations benefit more from EGFR-TKIs than from standard platinum-based chemotherapy at least in terms of response rate (RR), progression-free survival (PFS), toxicity profile and quality of life [7,8,9,10,11,12]. The aim of the present paper is to analyze the role of K-RAS mutations in NSCLC
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