On the pharmacogenetics of non-small cell lung cancer treatment

Abstract

Introduction. Despite many clinical efforts, non-small-cell lung cancer (NSCLC) has a dismal 5-year survival rate of 16%, and high incidence of recurrence. The success of biologically targeted agents, as well as the activity of well-established chemotherapeutic regimens, has been limited by inherited/ acquired resistance, and biomarkers to adapt the prescription of anticancer drugs to patients' features are urgently warranted. Areas covered. In oncology, pharmacogenetics should provide the way to select patients who may benefit from a specific therapy that best match the individual and tumor genetic profile, thus allowing maximum activity and minimal toxicity. The present review summarizes the main findings on NSCLC pharmacogenetics, critically reappraising the most important studies on polymorphisms correlated with outcome of pemetrexed and EGFR-inhibitors, and provides perspective on clinical application of genomic tests for treatment decision-making. Expert Opinion. A major challenge in NSCLC is the identification of subgroups of diseases/patients that will truly benefit from specific treatments. Ideally, convenient and minimally invasive tests to decipher biomarkers of chemosensitivity/resistance and toxicity should be developed alongside novel anticancer treatments. Integration with the latest generation of whole-genome analyses and liquid biopsies as well as prospective validation in large cohorts of patients will overcome the limitations of the traditional pharmacogenetic approaches. ARTICLE HISTORY

Pharmacogenetic Association between XRCC1 Polymorphisms and Response to Platinum-Based Chemotherapy in Asian Patients with NSCLC: A Meta-Analysis

“…Lung cancer can be histologically classified as non-small-cell lung cancer (NSCLC) and small cell lung cancer (SCLC). NSCLC, accounting for ~85% of all cases, includes several subtypes: squamous cell carcinoma, adenocarcinoma, large cell carcinoma, and the other subtypes 2 . The prognosis of lung cancer is usually poor since only a few patients can be early diagnosed and surgically treated with a good prognosis 3 .…”

Functional role of eukaryotic translation initiation factor 4 gamma 1 (EIF4G1) in NSCLC

“…Notably, NSCLC accounts for approximately 80%~85% of lung cancers [ 4 ]. Although the conventional treatment (surgery and chemotherapy) of NSCLC advances, NSCLC has a dismal 5-year survival rate of 16% due to the majority of patients present at the diagnosis with advanced stages [ 5 , 6 ], as well as high incidence of recurrence [ 7 ]. In recent years, better understanding of the molecular biology of NSCLC has led to a revolution in the treatment of these neoplasms [ 8 ].…”

Oridonin enhances the radiosensitivity of lung cancer cells by upregulating Bax and downregulating Bcl‑2

“…In recent years, great progress has been made in the diagnosis of and clinical therapy for lung cancer. However, the mortality rate of patients with lung cancer remains high, with a 5-year survival rate of only 15% (25)(26)(27). Oridonin is a compound that is extracted from the traditional Chinese herb R. rubescens, which possesses anticancer properties through inhibiting proliferation and promoting apoptosis (24,28,29).…”