Prognostic and predictive biomarkers with therapeutic targets in nonsmall-cell lung cancer: A 2023 update on current development, evidence, and recommendation.

Background: Since the publication of the original work in 2014, significant progress has been made in the characterization of genomic alterations that drive oncogenic addiction of nonsmall cell lung cancer (NSCLC) and how the immune system can leverage non-oncogenic pathways to modulate therapeutic outcomes. This update evaluates and validates the recent and emerging data for prognostic and predictive biomarkers with therapeutic targets in NSCLC.

Data Sources: We performed a literature search from January 2015 to October 2023 using the keywords , , , , , , , and .

Study Selection And Data Extraction: We identified, reviewed, and evaluated relevant clinical trials, meta-analyses, seminal articles, and published clinical practice guidelines in the English language.

Data Synthesis: Regulatory-approved targeted therapies include those somatic gene alterations of ("classic" mutations, exon 20 insertion, and rare mutations), , , , , , , , and . Data for immunotherapy and circulating tumor DNA in next-generation sequencing are considered emerging, whereas the predictive role for gene mutation is insufficient.

Conclusions: Advances in sequencing and other genomic technologies have led to identifying novel oncogenic drivers, novel resistance mechanisms, and co-occurring mutations that characterize NSCLC, creating further therapeutic opportunities. The benefits associated with immunotherapy in the perioperative setting hold initial promise, with their long-term results awaiting.