NEWARK, DE — CorriXR Therapeutics announced new peer-reviewed findings showing that its CRISPR-based gene-editing approach can resensitize squamous cell lung carcinoma (LUSC) tumors to standard chemotherapy, offering a potential path to overcoming one of oncology’s most persistent challenges: treatment resistance.
The study, published in Molecular Therapy Oncology and conducted in collaboration with ChristianaCare’s Gene Editing Institute (GEI), evaluated whether disabling NRF2 — a key regulator of cellular stress responses — could reverse chemoresistance in LUSC. NRF2 overactivation is known to allow tumors to survive and adapt under therapeutic pressure, limiting the effectiveness of chemotherapy in a large subset of cancers.
CorriXR reported that editing as little as 20% to 40% of tumor cells to disrupt NRF2 was enough to restore chemosensitivity and slow tumor growth in preclinical models. The approach also reduced NRF2 expression and downstream signaling markers, demonstrating successful pathway disruption. Off-target edits remained below 0.2%, a threshold the company said supports the specificity and safety of its CRISPR system.
Eric B. Kmiec, Ph.D., founder and CEO of CorriXR and executive director of GEI, said the results reinforce the company’s strategy of disrupting cancer-survival pathways rather than developing entirely new therapeutic classes. “We are encouraged by the consistency of results across in vitro human lung cancer models and our in vivo studies and are actively pursuing IND-enabling work to bring this promising approach to patients,” he said.
The study also highlights the effectiveness of the lipid nanoparticle delivery system used to transport the CRISPR machinery into tumor cells. The system demonstrated strong performance in both engineered and patient-derived models, a result the company said bolsters the program’s path toward clinical development.
Kelly Banas, Ph.D., lead author and associate director of research at GEI, said targeting NRF2 may help reduce chemotherapy doses, lower toxicity, and keep patients healthier through treatment. “Treatment resistance remains one of the greatest challenges in oncology,” she said. “These data show that targeting NRF2 can meaningfully resensitize tumors with minimal unintended effects.”
While the study focused on LUSC, the team noted that NRF2-driven resistance is common across several solid tumors, including head and neck squamous cell carcinoma (HNSCC), esophageal cancer, and liver cancers. CorriXR said the findings support advancement of both its HNSCC and LUSC programs toward clinical trials.
The company and GEI are currently validating the results through independent contract research organizations and preparing regulatory studies for a planned Investigational New Drug application to the U.S. Food and Drug Administration. CorriXR is also exploring partnerships to accelerate clinical translation.
The full study, Functional characterization of tumor-specific CRISPR-directed gene editing as a combinatorial therapy for the treatment of solid tumors, is available through Molecular Therapy Oncology.
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