The treatment of non-small-cell lung cancer (NSCLC) has made significant progress in recent years through the use of immune checkpoint inhibitors (ICIs). Nevertheless, many patients either do not respond to this therapy at all or develop resistance over the course of treatment. The causes include a complex interplay of biological characteristics of the tumor, changes in its microenvironment, and patient-specific factors such as an altered gut microbiome.
The journal Nature Reviews Clinical Oncology has now published the article “Treatment of NSCLC after chemoimmunotherapy — are we making headway?”, co-authored by the Scientific Coordinators of the DZL Disease Area Lung Cancer, Prof. Dr. Martin Reck (ARCN) and ILH Scientist Prof. Dr. Rajkumar Savai (UGMLC). This review highlights the current challenges in treating NSCLC with ICIs and presents new research approaches aimed at overcoming resistance mechanisms.
A common endpoint of many resistance mechanisms is an immunosuppressive tumor microenvironment that blocks the effectiveness of therapy. To address these barriers, a range of approaches is currently under investigation: antibody-based therapies (e.g., bispecific antibodies or antibody–drug conjugates), targeted drugs, adoptive cell therapies, vaccines, and new forms of immunotherapy administered directly into the tumor.
At the same time, researchers are working intensively to identify biomarkers that could help predict which patients will benefit from which therapies. Although the clinical relevance of many biomarkers remains uncertain, adaptive, biomarker-driven studies may in the future contribute to a better understanding of resistance mechanisms and enable the faster clinical translation of new treatment approaches.
The latest research shows: despite ongoing challenges, the combination of innovative therapeutic strategies and precise diagnostics opens up new perspectives for people with advanced NSCLC.
Source: Nature Reviews Clinical Oncology - doi.org/10.1038/s41571-025-01061-7
