Title:Genotype Driven Therapy for Non-Small Cell Lung Cancer: Resistance, Pan Inhibitors and Immunotherapy
Volume: 27
Issue: 32
Author(s): Sitanshu S. Singh, Achyut Dahal, Leeza Shrestha and Seetharama D. Jois*
Affiliation:
- School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, Monroe LA 71201,United States
Keywords:
Non-small Cell Lung Cancer (NSCLC), EGFR, HER2, KRAS, ALK, resistance, Tyrosine Kinase
Inhibitors (TKIs), PD-1-PD-L1.
Abstract: Eighty-five percent of patients with lung cancer present with Non-small Cell Lung Cancer
(NSCLC). Targeted therapy approaches are promising treatments for lung cancer. However, despite the
development of targeted therapies using Tyrosine Kinase Inhibitors (TKI) as well as monoclonal antibodies,
the five-year relative survival rate for lung cancer patients is still only 18%, and patients inevitably
become resistant to therapy. Mutations in Kirsten Ras Sarcoma viral homolog (KRAS) and epidermal
growth factor receptor (EGFR) are the two most common genetic events in lung adenocarcinoma;
they account for 25% and 20% of cases, respectively. Anaplastic Lymphoma Kinase (ALK) is a transmembrane
receptor tyrosine kinase, and ALK rearrangements are responsible for 3-7% of NSCLC, predominantly
of the adenocarcinoma subtype, and occur in a mutually exclusive manner with KRAS and
EGFR mutations. Among drug-resistant NSCLC patients, nearly half exhibit the T790M mutation in
exon 20 of EGFR. This review focuses on some basic aspects of molecules involved in NSCLC, the development
of resistance to treatments in NSCLC, and advances in lung cancer therapy in the past ten
years. Some recent developments such as PD-1-PD-L1 checkpoint-based immunotherapy for NSCLC
are also covered.
