On January 22, 2026 CorriXR Therapeutics, an oncology focused biotherapeutics company developing genetic medicines to overcome drug resistance in solid tumors, reported that its novel CRISPR-directed disruption of the transcription factor NRF2 can restore chemosensitivity in head and neck and esophageal squamous cell carcinoma models. The preclinical data were published in Molecular Therapy Oncology. The study, conducted in collaboration with scientists at ChristianaCare’s Gene Editing Institute (GEI), reinforces CorriXR’s previously reported data in lung cancer models and highlights how CRISPR targeting of NRF2 can disrupt tumor cells’ protective mechanisms and potentially boost patients’ bodies’ ability to respond more effectively to standard chemotherapy.

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"For patients with solid tumor cancers, once their tumors become resistant to chemotherapy, treatment options narrow and are often more toxic to them," said Eric B Kmiec, Ph.D., Founder and Chief Executive Officer of CorriXR Therapeutics and Executive Director of GEI. "These data from CorriXR’s first-in-class editing approach suggest that by precisely disrupting NRF2, we may be able to reopen the window to standard treatments and potentially do so at lower doses; this could translate into better control of disease with fewer side effects for patients."

NRF2 is a master regulator of cellular stress responses and a well-established driver of treatment resistance in multiple cancers, making it an attractive but historically "undruggable" target for therapeutic intervention. CorriXR is advancing essential studies to support an IND filing in head and neck squamous cell carcinoma (HNSCC) as a potential first clinical indication.

Head and neck cancer, 90% of which is HNSCC, is the seventh most diagnosed cancer worldwide, with annual incidence predicted to reach one million new cases by 2030. With 50% of patients experiencing recurrence within two years, there is a significant need for new approaches that can overcome resistance to current treatment paradigms. CorriXR anticipates completion of additional in vivo studies in HNSCC in combination with chemotherapy and radiation in the first half of 2026.

Study Overview

Researchers used CRISPR/Cas9 complexes to disrupt NRF2 in hypopharyngeal (FaDu) and esophageal (KYSE‑410) squamous cell carcinoma cells and then assessed gene editing outcomes, NRF2 pathway activity, and response to cisplatin and 5‑fluorouracil. Key study findings include:

High levels of on-target editing produced substantial reductions in NRF2 protein levels, decreased expression of downstream stress response genes, and significantly restored chemosensitivity.
Genetic disruption of NRF2 alone is sufficient to disrupt its ability to activate the genes that defend tumor cells.
Enhanced chemosensitivity after NRF2 disruption persisted over time, creating a treatment window for combination therapy.
The choice of CRISPR editing site on NRF2 influences both the functional impact on NRF2 and which cells are affected by the edit. Editing that disrupts a functional binding domain enables an approach that is agnostic to and independent of genetic mutations in the cancer cells.
"These findings complement previously published data from CorriXR and GEI showing that tumor-specific NRF2 editing in lung cancer models can resensitize tumors to standard chemotherapy and reduce tumor growth in vivo, thereby reinforcing NRF2 as a central node for overcoming drug resistance," said Natalia Rivera-Torres, Ph.D., lead author of the study and Associate Director of Research at GEI.

Kmiec added, "What is most encouraging about this work is that we are giving existing drugs a second chance to work in tumors that have learned how to evade them, enabling patients to benefit more, and longer, from proven regimens, with a better quality of life."

(Press release, CorriXR Therapeutics, JAN 22, 2026, View Source [SID1234662176])