CorriXR Therapeutics Publishes Peer-Reviewed Preclinical Study Demonstrating CRISPR-Based NRF2 Editing Restores Chemosensitivity in Treatment-Resistant Solid Tumors
CorriXR Therapeutics, an oncology-focused biotherapeutics company developing next-generation genetic medicines to overcome drug resistance in solid tumors, has announced the publication of new peer-reviewed preclinical data demonstrating that targeted CRISPR gene editing of NRF2 can resensitize treatment-resistant cancers to standard chemotherapy. The findings were published in Molecular Therapy Oncology and provide compelling additional evidence supporting NRF2 as a critical driver of chemotherapy resistance across multiple solid tumor types.
The newly published study shows that CorriXR’s mutation-agnostic, CRISPR-directed disruption of NRF2 restores responsiveness to commonly used chemotherapies in head and neck squamous cell carcinoma (HNSCC) and esophageal squamous cell carcinoma models. These results build on CorriXR’s previously reported work in lung cancer models and further validate NRF2 as a central molecular node responsible for tumor survival under therapeutic stress.
The study was conducted in collaboration with scientists at ChristianaCare’s Gene Editing Institute (GEI), reinforcing the strength of the partnership between CorriXR and one of the nation’s leading academic centers for gene editing research.
Addressing a Major Challenge in Cancer Care: Chemotherapy Resistance
Chemotherapy resistance remains one of the most significant barriers to durable cancer control. While many patients initially respond to standard chemotherapeutic regimens, tumors frequently evolve mechanisms to evade treatment, rendering subsequent therapies less effective and often more toxic. Once resistance emerges, treatment options narrow considerably, leading to poorer outcomes and diminished quality of life for patients.
At the center of this problem is NRF2 (nuclear factor erythroid 2-related factor 2), a transcription factor that regulates cellular responses to oxidative stress. Although NRF2 plays a protective role in healthy cells, many cancers exploit this pathway to shield themselves from chemotherapy-induced damage. Elevated NRF2 activity enables tumor cells to neutralize reactive oxygen species, repair DNA damage, and survive under conditions that would otherwise be lethal.
Despite being widely recognized as a key driver of therapy resistance, NRF2 has historically been considered “undruggable” using traditional small-molecule or antibody-based approaches. CorriXR’s work challenges this long-standing limitation by applying precise CRISPR-based gene editing to directly disrupt NRF2 function at the genetic level.
Key Findings from the Molecular Therapy Oncology Study
In the newly published study, researchers employed CRISPR/Cas9 ribonucleoprotein complexes to disrupt NRF2 in hypopharyngeal (FaDu) and esophageal (KYSE-410) squamous cell carcinoma cell lines. These models were selected because both cancer types frequently develop resistance to platinum-based and fluoropyrimidine chemotherapies, representing an urgent unmet clinical need.
Following NRF2 editing, the investigators evaluated editing efficiency, downstream NRF2 pathway activity, and tumor cell responses to the chemotherapies cisplatin and 5-fluorouracil (5-FU). The results demonstrated several key findings:
High levels of on-target gene editing led to substantial reductions in NRF2 protein expression, accompanied by decreased activation of NRF2-dependent stress response genes. As a result, tumor cells lost critical protective mechanisms that normally enable them to withstand chemotherapy-induced damage.
Importantly, genetic disruption of NRF2 alone was sufficient to significantly restore chemosensitivity. Edited cancer cells exhibited markedly increased susceptibility to cisplatin and 5-FU compared with unedited controls, confirming that NRF2 activity is a primary driver of resistance rather than a secondary or compensatory pathway.
The restored chemosensitivity persisted over time, suggesting that NRF2 editing creates a durable therapeutic window during which standard chemotherapy regimens can regain effectiveness. This finding supports the potential for combination strategies in which gene editing is paired with existing drugs rather than replacing them.
The study also revealed that the specific CRISPR editing site within the NRF2 gene influences both functional outcomes and the subset of cells affected. Targeting regions critical for NRF2’s transcriptional activity—particularly domains involved in DNA binding—enabled disruption of NRF2 signaling in a manner that was independent of underlying cancer-specific mutations. This mutation-agnostic approach broadens the potential applicability of CorriXR’s strategy across genetically diverse tumors.
Reinforcing Prior Evidence Across Multiple Tumor Types
These findings complement previously published data from CorriXR and GEI demonstrating that tumor-specific NRF2 editing in lung cancer models can resensitize tumors to standard chemotherapy and reduce tumor growth in vivo,” said Natalia Rivera-Torres, Ph.D., lead author of the study and Associate Director of Research at ChristianaCare’s Gene Editing Institute. “Together, these results reinforce NRF2 as a central and actionable target for overcoming drug resistance in solid tumors.”
By demonstrating consistent effects across lung, head and neck, and esophageal cancer models, the research suggests that NRF2-driven resistance represents a shared vulnerability across multiple tumor types. This raises the possibility that CorriXR’s approach could form the basis of a platform strategy applicable to a broad range of solid tumors.
Clinical Implications and Path Toward the Clinic
For patients with solid tumor cancers, once their tumors become resistant to chemotherapy, treatment options narrow and are often more toxic,” said Eric B. Kmiec, Ph.D., Founder and Chief Executive Officer of CorriXR Therapeutics and Executive Director of the Gene Editing Institute. “These data suggest that by precisely disrupting NRF2, we may be able to reopen the window to standard treatments—and potentially do so at lower doses.”
Lower chemotherapy doses could translate into fewer side effects, improved tolerability, and better overall quality of life for patients. Rather than introducing entirely new cytotoxic agents, CorriXR’s strategy aims to give proven therapies a “second chance” to work by dismantling the tumor’s defense systems.
NRF2’s role as a master regulator of cellular stress responses has long made it an attractive therapeutic target, but conventional drug development approaches have failed to effectively inhibit it. CRISPR-based gene editing offers a fundamentally different solution by directly disabling the gene itself, bypassing the limitations of protein-based inhibition.
Focus on Head and Neck Squamous Cell Carcinoma
CorriXR is currently advancing essential preclinical studies to support an Investigational New Drug (IND) filing in head and neck squamous cell carcinoma as a potential first clinical indication. HNSCC accounts for approximately 90% of head and neck cancers and represents a significant global health burden.
Head and neck cancer is the seventh most commonly diagnosed cancer worldwide, with annual incidence projected to approach one million new cases by 2030. Despite advances in surgery, radiation, and systemic therapies, outcomes remain poor for many patients. Approximately half of patients experience disease recurrence within two years of initial treatment, often with tumors that are resistant to standard therapies.
This high recurrence rate underscores the urgent need for new approaches capable of overcoming treatment resistance. CorriXR’s NRF2-targeted gene editing strategy directly addresses this unmet need by targeting a core mechanism of tumor survival.
Next Steps and Future Outlook
CorriXR anticipates completing additional in vivo studies in HNSCC models in combination with chemotherapy and radiation therapy in the first half of 2026. These studies will further evaluate the safety, durability, and therapeutic benefit of NRF2 editing in clinically relevant settings.
“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,” Kmiec added. “This approach could enable patients to benefit more—and longer—from proven treatment regimens, while potentially reducing toxicity and improving quality of life.”
As CorriXR advances toward clinical development, the newly published data in Molecular Therapy Oncology provide a strong scientific foundation for its first-in-class gene editing approach. By targeting NRF2, CorriXR aims to redefine how drug resistance is treated in solid tumors and open new therapeutic possibilities for patients who currently face limited options.
About CorriXR Therapeutics
CorriXR is developing genetic medicines to transform the treatment of solid tumors. The Company’s patented non-viral gene editing platform targets NRF2, a transcription factor controlling more than 200 genes that shape a pro-oncogenic tumor microenvironment and drive treatment resistance. Disruption of NRF2 resensitizes cancer cells to standard-of-care therapies. CorriXR platform is being developed for potential use as a monotherapy or in combination with chemotherapy, radiotherapy, or immunotherapy. The platform has potential applications across more than 30 types of squamous cell carcinomas by improving innate immunity, increasing treatment efficiency at lower doses, expanding patient eligibility, and reducing treatment-limiting toxicity — ultimately leading to improved patient outcomes.
About ChristianaCare Gene Editing Institute
ChristianaCare is one of the largest healthcare systems in the Mid-Atlantic region. Within its Helen F. Graham Cancer Center & Research Institute, ChristianaCare established the Gene Editing Institute in 2015 as a leading center for translational research in gene editing technologies. CorriXR is the inaugural biotech spin-out of ChristianaCare and the Gene Editing Institute, which served as the research engine behind CorriXR. This collaboration combines deep scientific expertise with direct access to clinical environments, enabling CorriXR to accelerate the development and commercialization of next-generation therapies
