EGFR and KRAS Mutations, and ALK Fusions: Current Developments and Personalized Therapies for Patients with Advanced Non-Small-Cell Lung Cancer

Abstract

Personalized therapy has significantly developed in lung cancer treatment over recent years. VEGF and EGF play a major role in non-small-cell lung cancer (NSCLC) tumor angiogenesis and aggressiveness. EGFR mutation as well as KRAS and ALK rearrangements are important biomarkers in the field owing to potential targeted therapies involved in clinical practice: erlotinib, geftinib, cetuximab and crizotinib. More recently, regulation of tumor immunity through CTLA4 and PD1/L1 has emerged as a promising field in NSCLC management. This review will focus on the current and future biomarkers in the advanced NSCLC field and also address potential related targeted therapies for these patients.

Learning from biomedical linked data to suggest valid pharmacogenes

“…For instance, it is widely known that aberrant epidermal growth factor receptor (EGFR) signaling lead to various oncogenic phenotypes [56] and previous PGx invetigations have shown that the EGFR gene mutation status was associated with EGFR-targeted agents efficacy such as Erlotinib’s (rank 2) in the case of non-small cell lung cancer (NSCLC) [56, 57]. In addition to its single agent activity, it has also been shown that this tyrosine kinase inhibitor acts in synergy with standard chemotherapy such as Fluorouracil in various cancer patients [58, 59] and we were able to pair Fluorouracil with the EGFR gene as well (rank 3).…”

Bringing Next-Generation Sequencing Oncology Tests into the Diagnostic Setting

“…For example, somatic mutations in EGFR inform the prescription of drugs (such as erlotinib and gefitinib) targeting the gene product, a tyrosine kinase [9,10]. However, detecting rare (yet clinically actionable) somatic mutations has been very challenging using conventional methods such as Sanger sequencing.…”

TG4010 immunotherapy: a novel weapon against advanced non-small cell lung cancer?

“…Until the 1980s, treatment generally yielded poor outcomes (2), and prognosis was only good for early stages of operable disease. However, advances in targeted molecular therapy since 2005 have brought new hope to patients with advanced NSCLC, especially those harboring the epidermal growth factor receptor (EGFR) mutation in exons 18, 19 and 21 (3).…”

“…However, advances in targeted molecular therapy since 2005 have brought new hope to patients with advanced NSCLC, especially those harboring the epidermal growth factor receptor (EGFR) mutation in exons 18, 19 and 21 (3). As a result, the median overall survival (OS) of a small group of patients with advanced NSCLC increased from 10 to 18-36 months (2). The fusion of the EML4 gene (echinoderm microtubuleassociated protein-like 4) and the ALK gene (anaplastic lymphoma kinase) affects the outcome of almost 5% of patients with this phenotype (2,4).…”

“…As a result, the median overall survival (OS) of a small group of patients with advanced NSCLC increased from 10 to 18-36 months (2). The fusion of the EML4 gene (echinoderm microtubuleassociated protein-like 4) and the ALK gene (anaplastic lymphoma kinase) affects the outcome of almost 5% of patients with this phenotype (2,4). Indeed, patients with this profile presented a very good overall response rate (74%) when submitted to treatment with crizotinib (an ALK-inhibitor) in the clinical trial PROFILE 1014 (5).…”