Updates in Pharmacogenetics of Non-Small Cell Lung Cancer

Abstract

Though significant clinical advances have been made, lung cancer remains the most lethal, with a low 5-year survival rate. The variability in patient response towards therapy is substantial and is associated with lung cancer’s genomic landscape. Pharmacogenetic studies have deciphered many clinically relevant associations between tumor genetic alterations and their influences on drug efficacy, toxicity sensitivity and overall outcomes of cancer treatment. Biomarkers are tools in the arsenal that can help in the prediction, prognosis, diagnosis and follow-up of cancer treatment. Bulk and single-cell next-generation sequencing of large patient cohorts have generated a better understanding of the genetic underpinnings of lung cancer, and opening up personalized therapeutic opportunities. Immunotherapy and personalized medicine are providing hope for lung cancer patients. This review highlights the genetic alterations and important lung cancer biomarkers. The pharmacogenetic associations, personalized immunotherapy and challenges associated with effective therapy are also discussed. Pharmacogenetics and pharmacogenomics can open up new vistas for optimized, personalized NSCLC treatment.

Challenges in the Use of Targeted Therapies in Non–Small Cell Lung Cancer

“…Pharmacogenomics is an evolving branch of pharmacology and seeks to understand the association between genetics, response rates and toxicities [ 130 ]. It is an individual variation in drug toxicity and efficacy related to inherited variations in drug transport, metabolism and target enzymes.…”

“…A major challenge to incorporating pharmacogenetics into routine NSCLC care include establishing validation and standardization of genotyping procedures to consistently include the genotyping of normal tissue from each patient and not focus only on tumor tissue [ 130 ]. This could help identify germ-line polymorphisms of clinical relevance in each patient.…”