Frontiers of ctDNA, targeted therapies, and immunotherapy in non-small-cell lung cancer

Area of Science:

• Oncology
• Molecular Diagnostics
• Cancer Therapeutics

Background:

• Non-small-cell lung cancer (NSCLC) remains a leading cause of cancer mortality globally.
• Circulating tumor DNA (ctDNA), tyrosine kinase inhibitors (TKIs), and immunotherapy have significantly advanced NSCLC diagnosis and treatment.
• ctDNA offers precise and convenient methods for clinical decision-making, enhancing patient quality of life.

Purpose of the Study:

• To review current methods for ctDNA detection and their influence on therapeutic strategies in NSCLC.
• To discuss targeted therapies (TKIs) for EGFR and ALK mutations and emerging resistance mechanisms.
• To explore the role of immune checkpoint inhibitors (ICIs) in immunotherapy and blood tumor mutational burden (bTMB) as a biomarker.

Main Methods:

• Review of current literature on ctDNA detection techniques.
• Analysis of TKI therapies targeting EGFR and ALK mutations (e.g., osimertinib, lorlatinib).
• Examination of immunotherapy agents targeting PD-1, PD-L1, and CTLA-4.
• Evaluation of ctDNA-based blood tumor mutational burden (bTMB) as a predictive biomarker.

Main Results:

• ctDNA quantification provides precision in clinical decision-making for NSCLC.
• TKI-based targeted therapies and immunotherapies have improved NSCLC patient outcomes.
• Emerging resistance mechanisms to targeted therapies require ongoing investigation.
• bTMB calculated via ctDNA assays shows promise as a biomarker for immunotherapy response.

Conclusions:

• Advances in ctDNA detection, targeted therapies, and immunotherapy have revolutionized NSCLC management.
• Despite progress, challenges persist, highlighting the need for continued research and clinical trials.
• Developing more effective drugs and therapeutic strategies is crucial for improving survival and quality of life for NSCLC patients.