Current and Future Targeted Therapies for Non-small-cell Lung Cancers With Aberrant EGF Receptors

Shanthi Kanthala; Sandeep Pallerla; Seetharama Jois


Future Oncol. 2015;11(5):865-878. 

In This Article

EGFR Detection Methods

Studies suggest that EGFR TKIs produce a promising response in patients with NSCLC harboring EGFR mutations; hence, the detection of somatic EGFR tyrosine kinase domain mutations has gained importance. Various molecular predictive detection methods such as DNA sequencing, immunohistochemistry, PCR, and Therascreen® (QIAGEN, CA, USA) EGFR RGQ PCR mutation kit are commercially available. Some of these methods have limitations in terms of detection of EGFR mutation. For example, the immunohistochemistry method failed to detect an uncommon EGFR mutation, resistance mutation T790M in exon 20, and failed to predict patient response to EGFR TKIs. The EGFR29 mutation kit from Qiagen is one of those commercially available in the market that can detect the 29 most frequently found EGFR mutations against a background of wild type genomic DNA. Cobas® (Roche Molecular Diagnostics, CA, USA) EGFR mutation test is the first FDA-approved test for mutations in NSCLC.[37,38]

Lung cancer therapy will involve screening patients for biomarkers.[39–42] However, there are controversies regarding the screening procedures. The National Cancer Institute initiated the National Lung Screening Trial in 2002. This involved randomized clinical trials that screened high-risk individuals with low-dose CT scan or standard chest radiography. The results from this trial produced a 20% reduction in mortality rates.[43–45] Such screening involves questions such as who should be considered as high-risk patients for screening, the effectiveness of screening, the risks associated with radiation, adverse events from additional diagnostic testing and the effects of false-positive results. However, such screenings may be necessary since TKIs and chemotherapeutic agents may do more harm than good if not treated with proper strategies.