Testing for EGFR Mutations and ALK Rearrangements in Advanced Non-Small-Cell Lung Cancer: Considerations for Countries in Emerging Markets

Abstract

The treatment of patients with advanced non-small-cell lung cancer (NSCLC) in recent years has been increasingly guided by biomarker testing. Testing has centered on driver genetic alterations involving the epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) rearrangements. The presence of these mutations is predictive of response to targeted therapies such as EGFR tyrosine kinase inhibitors (TKIs) and ALK TKIs. However, there are substantial challenges for the implementation of biomarker testing, particularly in emerging countries. Understanding the barriers to testing in NSCLC will be key to improving molecular testing rates worldwide and patient outcomes as a result. In this article, we review EGFR mutations and ALK rearrangements as predictive biomarkers for NSCLC, discuss a selection of appropriate tests and review the literature with respect to the global uptake of EGFR and ALK testing. To help improve testing rates and unify procedures, we review our experiences with biomarker testing in China, South Korea, Russia, Turkey, Brazil, Argentina and Mexico, and propose a set of recommendations that pathologists from emerging countries can apply to assist with the diagnosis of NSCLC.

Cancer-Testis Antigen LDH-C4 in Tissue, Serum, and Serum-Derived Exosomes Serves as a Promising Biomarker in Lung Adenocarcinoma

“…Advancements in pathophysiological understanding have increased the array of treatment options for local and advanced disease, leading to individual treatment plans. Advancements in pathophysiological understanding of molecular targeted therapy and immunotherapy (5), such as epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), have improved the prognosis of LUAD patients (21), while a considerable number of LUAD still lack specific targets. Previous studies have shown that LDH-C4, as an important tumor CTA, plays an important role in tumorigenesis and development (10)(11)(12)(13)(14)(15)19), acting as a potential target for tumor immunotherapy (22).…”

A narrative review of methods for the identification of ALK fusions in patients with non-small cell lung carcinoma

“…The most frequently used tissue assays that are currently available to identify ALK fusions include both traditional single methodologies such as immunohistochemistry (IHC), break-apart fluorescence in situ hybridization (FISH) and real-time PCR, as well as the increasingly popular NGS ( 42 - 51 ). Each of these approaches has advantages and disadvantages that need to be carefully balanced to design sensible testing algorithms.…”

The Importance of Screening for EGFR Mutation in Lung Cancer

“…Targeted NGS Panels are helpful for finding different mutations, such as T790M, and are capable of sequencing numerous genes at once. They are useful for comprehending the larger genetic profile of a patient's tumor of their great sensitivity and comprehensiveness [18].…”

“…On the other hand, T790M and other gene amplifications and mutations can be found in tissue samples using EGFR T790M FISH Probes. Fluorescently labeled probes that bind to particular DNA sequences are used in FISH [18].…”