Published in Molecular Therapy Oncology, this study provides hope that overcoming drug resistance-a major barrier in cancer treatment-may soon be within reach.
The research focused on lung squamous cell carcinoma, a fast-progressing type of non-small cell lung cancer that accounts for 20-30% of lung cancer cases. Scientists engineered lung cancer cells carrying a tumor-specific NRF2 mutation called R34G.
Using CRISPR/Cas9, they selectively disrupted the mutated NRF2 gene, leaving healthy cells unaffected. This genetic knockout re-sensitized cancer cells to standard chemotherapy drugs like carboplatin and paclitaxel, slowing tumor growth in lab cultures and animal models.
Remarkably, editing just 20-40% of tumor cells yielded significant therapeutic effects, a promising feature for clinical application where complete gene modification is challenging. Tumors treated with CRISPR showed reduced NRF2 activity and better response to chemotherapy without detected off-target genetic damage.
Lead author Dr. Kelly Banas emphasized that targeting NRF2 through gene editing could augment existing therapies, reducing drug resistance and allowing patients to tolerate treatment longer with improved outcomes. Since NRF2 also mediates chemoresistance in liver, esophageal, and head and neck cancers, this approach may have broad implications.
While these preclinical results are compelling, clinical trials are necessary to confirm safety and effectiveness in humans. If successful, CRISPR-based NRF2 targeting could redefine cancer treatment by restoring the power of conventional chemotherapy and prolonging patient survival.
This study exemplifies how precision gene editing can tackle one of oncology’s toughest challenges-drug resistance-offering new hope to patients facing aggressive tumors.
REFERENCE: Kelly H. Banas, Pawel A. Bialk, Natalia Rivera-Torres, Katelynn Owens, Tori N. Reiner, Kristen M. Pisarcik, Nicole Haas, Emily Gielda, Komal Khan, Krishna Priya Narra, Eric B. Kmiec. Functional characterization of tumor-specific CRISPR-directed gene editing as a combinatorial therapy for the treatment of solid tumors. Molecular Therapy Oncology, 2025; 33 (4): 201079 DOI: 10.1016/j.omton.2025.201079.
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