Emerging Biomarkers in Personalized Therapy of Lung Cancer

Abstract

The two clinically validated and Food and Drug Administration approved lung cancer predictive biomarkers (epidermal growth factor receptor mutations and anaplastic lymphoma kinase (ALK) translocations) occur in only about 20 % of lung adenocarcinomas and acquired resistance develops to first generation drugs. Several other oncogenic drivers for lung adenocarcinoma have emerged as potentially druggable targets with new predictive biomarkers. Oncologists are requesting testing for ROS1 translocations which predict susceptibility to crizotinib, already approved for ALK positive lung cancers. Other potential biomarkers which are currently undergoing clinical trials are RET, MET, HER2 and BRAF. Detection of these biomarkers includes fluorescent in situ hybridization and/or reverse transcriptase polymerase chain reaction (ROS1, RET, HER2), mutation analysis (BRAF) and immunohistochemistry (MET). Screening by immunohistochemistry may be useful for some biomarkers (ROS1, BRAF). Targeted next generation sequencing techniques may be useful as well. These five biomarkers are under consideration for inclusion in revised lung cancer biomarker guidelines by the College of American Pathologists, International Association for the Study of Lung Cancer and Association for Molecular Pathology.

Diagnostic MicroRNA Biomarker Discovery for Non-Small-Cell Lung Cancer Adenocarcinoma by Integrative Bioinformatics Analysis

“…The NSCLS adenocarcinoma is reported associated with the aberrations like the epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) fusion or rearrangement [3, 5], and several drugs such as gefitinib, erlotinib, and afatinib were developed for the targeting the aberrant gene products, but only few patients are ideal for the targeted treatments [6]. In addition, the patients treated with these target drugs may acquire resistance and make the treatment invalid [7]. There are also other aberrations reported associated with the NSCLC adenocarcinoma, such as mutations or fusions happen in HER2, BRAF, NF1, MEK1, RET, ROS1, and other genes.…”

“…With the coming of aging era and the air pollution in the developing countries, the incidence of lung cancer will keep high, and the early diagnosis of lung cancer becomes very necessary. However, we still lack sensitive and precision biomarkers for the early diagnosis or the personalized therapy of the lung cancer [7, 12, 13]. …”

Increased serum amyloid A as potential diagnostic marker for lung cancer: a meta-analysis based on nine studies

“…This is a consistent opinion that early diagnosis and individualized therapy are conducive to improve the prognosis of lung cancer [2]. Many studies have demonstrated that abnormal protein expressions and gene mutations are correlated with the ontogenesis and progression of lung cancer [2], and reliable biomarkers derived from these abnormal molecules are more likely to help make the medical decision for individualized therapy [3].…”

Successful ceritinib treatment in a man with MPE and an ALK fusion gene mutation after multiple treatments

“…So, targeted therapy is the trend of the development of lung cancer. However, two clinically validated and FDA approved lung cancer predictive biomarkers (EGFR and ALK translocations) occur in only about 20% of lung adenocarcinomas and acquired resistance develops to first generation drugs (Cagle et al 2016). More biomarkers and targeted drugs should be found.…”