NEWARK, DE — New preclinical research from CorriXR Therapeutics suggests a novel gene-editing strategy could reopen the door to standard chemotherapy for patients whose cancers have become resistant to treatment, a long-standing and often deadly challenge in oncology.
The findings, published in Molecular Therapy Oncology, show that CorriXR’s CRISPR-directed disruption of the transcription factor NRF2 restored chemosensitivity in head and neck and esophageal squamous cell carcinoma models. The study was conducted in collaboration with scientists at the ChristianaCare Gene Editing Institute and builds on previously reported data in lung cancer models.
NRF2 is a master regulator of cellular stress responses and a known driver of chemotherapy resistance across multiple cancers. While it has long been considered an attractive target, it has also been widely viewed as “undruggable” using conventional therapies. CorriXR’s approach uses CRISPR/Cas9 gene editing to directly disrupt NRF2, disabling tumor cells’ protective mechanisms and making them vulnerable once again to standard drugs.
“For patients with solid tumors, once chemotherapy resistance sets in, options narrow quickly and often become more toxic,” said Eric B. Kmiec, founder and chief executive officer of CorriXR Therapeutics and executive director of the ChristianaCare Gene Editing Institute. He said the data suggest precise NRF2 disruption could allow standard treatments to work again, potentially at lower doses, improving disease control while reducing side effects.
In the study, researchers edited NRF2 in hypopharyngeal and esophageal squamous cell carcinoma cell lines and evaluated gene-editing outcomes, pathway activity, and responses to cisplatin and 5-fluorouracil. High levels of targeted editing sharply reduced NRF2 protein levels, suppressed downstream stress-response genes, and significantly restored sensitivity to chemotherapy. The enhanced response persisted over time, creating what researchers described as a renewed treatment window for combination therapy.
The work also showed that disrupting specific functional domains of NRF2 can neutralize its activity regardless of the underlying genetic mutations in the cancer cells, a finding that could broaden the therapy’s applicability across tumor types.
“These findings reinforce NRF2 as a central node in drug resistance,” said Natalia Rivera-Torres, lead author of the study and associate director of research at the ChristianaCare Gene Editing Institute. She said the results complement earlier lung cancer data demonstrating tumor-specific NRF2 editing can resensitize cancers to chemotherapy and reduce tumor growth in vivo.
CorriXR is advancing studies to support an investigational new drug filing in head and neck squamous cell carcinoma as a potential first clinical indication. Head and neck cancer, about 90% of which falls into this category, is the world’s seventh most diagnosed cancer, with global incidence projected to reach one million new cases annually by 2030. Roughly half of patients experience recurrence within two years, highlighting the need for new approaches that overcome treatment resistance.
The company expects to complete additional in vivo studies combining NRF2 editing with chemotherapy and radiation in the first half of 2026.
CorriXR Therapeutics is developing non-viral genetic medicines targeting NRF2 to resensitize tumors to standard-of-care therapies, either as standalone treatments or in combination with chemotherapy, radiotherapy, or immunotherapy. More information is available at www.corrixr.com.
The ChristianaCare Gene Editing Institute, founded in 2015 within the Helen F. Graham Cancer Center & Research Institute, serves as a translational research hub for gene-editing technologies and was the research engine behind CorriXR’s formation. Additional details can be found at www.geneeditinginstitute.com.
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