Non-Small Cell Lung Cancer as a Precision Oncology Paradigm: Emerging Targets and Tumor Mutational Burden (TMB)

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Non-small cell lung cancer (NSCLC) treatment has been revolutionized by precision oncology, particularly with EGFR tyrosine kinase inhibitors.
• The development of resistance to these inhibitors has highlighted the need to understand diverse resistance mechanisms.
• Advancements in molecular testing reveal new subsets of NSCLC with distinct therapeutic implications.

Purpose of the Study:

• To review emerging, potentially targetable alterations in NSCLC, focusing on RET, ERBB2 (HER2), MET, and KRAS.
• To discuss the current evidence and controversies surrounding tumor mutational burden (TMB) as a biomarker for immunotherapy selection in NSCLC.
• To highlight the evolving landscape of precision oncology in NSCLC.

Main Methods:

• Literature review of recent studies on NSCLC molecular alterations and biomarkers.
• Analysis of data regarding targeted therapies and immunotherapy efficacy.
• Examination of TMB testing methodologies and clinical utility.

Main Results:

• Identification of RET, ERBB2 (HER2), MET, and KRAS as key emerging targets in NSCLC.
• Evidence supporting TMB as a potential predictive biomarker for immunotherapy in NSCLC.
• Discussion of ongoing controversies and challenges in TMB assessment.

Conclusions:

• Precision medicine in NSCLC continues to evolve with the discovery of new actionable targets.
• TMB holds significant promise for guiding immunotherapy decisions in NSCLC.
• Further research is needed to standardize TMB testing and confirm its predictive value.