Testing modalities for ALK-driven lung cancer: A narrative review

Anaplastic lymphoma kinase (ALK) rearranged non-small-cell lung cancer (NSCLC) comprises a distinct molecular entity with a reported global prevalence of 5-7%. The development and rapid approvals of small molecule ALK tyrosine kinase inhibitors (TKIs) have led to the development of diagnostic strategies with robust methodology and superior attributes. Owing to myriad alterations which can be present in the ALK gene in NSCLC, it is important to understand the principal attributes as well as limitations of each to aid in optimal therapeutic decision making. To prepare this review, we used the keywords, "ALK detection," "ALK NGS," "ALK TKI," and "EML4 (echinoderm microtubule-associated protein-like 4)-ALK," to search within scientific databases like Scopus, PubMed, and Embase. We chose 55 articles that we identified from this search. Detection of ALK is an essential frontline diagnostic test as per all international and national recommendations. The various modalities available include immunohistochemistry, fluorescence in situ hybridization, reverse transcriptase polymerase chain reaction, and DNA/RNA-based next-generation sequencing. Each has its own advantages and limitations with respect to test metrics like sensitivity and specificity, as well as ease of use, availability, and cost. This is a detailed review of these various techniques and their attributes.