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In a major step forward for cancer care, researchers at ChristianaCare’s Gene Editing Institute have shown that disabling the NRF2 gene with CRISPR technology can reverse chemotherapy resistance in lung cancer. The approach restores drug sensitivity and slows tumor growth. The findings were published Nov. 13, 2025 in the online edition of Molecular Therapy Oncology.
This breakthrough stems from more than a decade of research by the Gene Editing Institute into the NRF2 gene, a known driver of treatment resistance. The results were consistent across multiple in vitro studies using human lung cancer cell lines and in vivo animal models.
“We’ve seen compelling evidence at every stage of research,” said Kelly Banas, Ph.D., lead author of the study and associate director of research at the Gene Editing Institute. “It’s a strong foundation for taking the next step toward clinical trials.”
Potential Beyond Lung Cancer
The study focused on lung squamous cell carcinoma, an aggressive and common form of non-small cell lung cancer (NSCLC) that accounts for 20% to 30% of all lung cancer cases, according to the American Cancer Society. It’s estimated that over 190,000 people in the U.S. will be diagnosed in 2025.
While the research centered on this cancer type, the implications are broader. Overactive NRF2 contributes to chemotherapy resistance in several solid tumors, including liver, esophageal and head and neck cancers. The results suggest a CRISPR-based strategy targeting NRF2 could help resensitize a wide range of treatment-resistant tumors to standard chemotherapy.
“This is a significant step toward overcoming one of the biggest challenges in cancer therapy — drug resistance,” Banas said. “By targeting a key transcription factor that drives resistance, we’ve shown that gene editing can re-sensitize tumors to standard treatment. We’re hopeful that in clinical trials and beyond, this is what will allow chemotherapy to improve outcomes for patients and could enable them to remain healthier during the entirety of their treatment regimen.”
Targeting a Master Switch for Resistance
The research zeroed in on a tumor-specific mutation, R34G, in the NRF2 gene, which acts as a master regulator of cellular stress responses. When overactive, NRF2 helps cancer cells withstand chemotherapy.
Using CRISPR/Cas9, the team engineered lung cancer cells with the R34G mutation and successfully knocked out NRF2. This restored sensitivity to chemotherapy drugs such as carboplatin and paclitaxel. In animal models, tumors directly treated with CRISPR to knockout NRF2 grew more slowly and responded better to treatment.
“This work brings transformational change to how we think about treating resistant cancers,” said Eric Kmiec, Ph.D., senior author of the study and executive director of the Gene Editing Institute. “Instead of developing entirely new drugs, we are using gene editing to make existing ones effective again.”
Editing Reaches Threshold Levels
One of the most promising discoveries was that disrupting NRF2 in just 20% to 40% of tumor cells, was enough to improve the response to chemotherapy and shrink tumors. This insight is particularly relevant for clinical use, where editing every cancer cell may not be feasible.
To test therapy in mice, the researchers used lipid nanoparticles (LNPs), a non-viral method with high efficiency and low risk of unintended, off-target effects. Sequencing confirmed that the edits were highly specific to the mutated NRF2 gene, with minimal unintended changes elsewhere in the genome.
“The power of this CRISPR therapy lies in its precision. It’s like an arrow that hits only the bullseye,” said Banas. “This level of specificity with minimal unanticipated genomic side effects offers real hope for the cancer patients who could one day receive this treatment.”
With the opening of a new cardiology practice at its Wilmington campus, ChristianaCare is bringing life-saving treatment for peripheral artery disease (PAD) closer to home for people who live in and around the city of Wilmington.
Peripheral artery disease happens when plaque builds up in the arteries and limits blood flow to the legs. This can cause pain, cramping and difficulty walking. If left untreated, it can lead to serious problems like limb loss, heart attack or stroke.
“We’re on a mission to improve the heart and vascular health of our community, and one of the key ways we do that is to identify where people need access to care and ensure that it’s convenient, high-quality and accessible. ChristianaCare’s expansion of cardiology services to the Wilmington campus has made it easier for patients in Wilmington and the surrounding community to receive excellent heart and vascular care,” said Kirk Garratt, M.D., MSc, medical director of the Center for Heart and Vascular Health. “Importantly, it’s part of a multi-disciplinary effort to bring a focus on PAD that includes vascular surgery and interventional radiology. We’re expanding those services in the Wilmington community, too.”
In Delaware, an estimated 45,000 to 50,000 people are living with PAD. The condition is more common among older adults and those with diabetes, high blood pressure or a history of smoking, all of which are widespread in the state. Because symptoms can be subtle, many people may not know they have it. That’s why awareness and early diagnosis are so important.
Anyone who experiences leg pain, numbness or slow-healing sores should talk with their doctor. A simple test can measure blood flow, and with the right treatment or lifestyle changes, people can ease symptoms and lower their risk of serious complications.
The new practice, located in the Gateway Building at Wilmington Hospital, 501 West 14th Street, 4th Floor, offers convenient access to diagnosis and treatment in the heart of the city. The practice is open on Wednesdays from 8 a.m. to 12 p.m., and hours will be adjusted based on patient demand.
Meet the Cardiologist: Dr. Vikashsingh Rambhujun Board-certified interventional cardiologist Vikashsingh Rambhujun, MBBS, has cared for ChristianaCare patients for more than a decade and now sees patients at the Wilmington practice.
Rambhujun earned his medical degree from SSR Medical College in Mauritius. He completed his residency in internal medicine at the NYU Grossman Long Island School in New York and did his fellowship in cardiovascular medicine and interventional cardiology at ChristianaCare. Rambhujun also spent a year doing interventional cardiology and endovascular medicine and interventions at Yale University Hospital in New Haven, Connecticut. His research has been published widely in medical journals.
Rambhujun aims to help patients manage PAD before it becomes advanced. When appropriate, he can perform minimally invasive catheter-based procedures to open blockages in the arteries.
“We have new patients with blockages that haven’t progressed to the point that they need a procedure, which is where we want to catch them,” Rambhujun said. “We can manage their cholesterol, blood pressure and other risk factors to prevent disease from progressing.”
When Rambhujun began practicing in Wilmington, he made it a priority to speak at local community meetings, raising awareness about the warning signs of heart and vascular disease. His message is simple but urgent: don’t wait; seek treatment early.
“We’re trying to help people keep their toes and feet,” he said. “When we treat blockages from peripheral artery disease, the difference can be dramatic,” he said. “Patients who once struggled to walk even a short distance because of pain can leave the hospital able to move freely again. Helping someone reclaim their basic freedoms to walk, stay active and enjoy life is incredibly rewarding.”
ChristianaCare today broke ground on its new Health Center at Middletown, marking a major milestone in bringing expanded, affordable and exceptional care to families in southern New Castle County and northern Kent County. The center is expected to open in spring 2027.
The $92.3 million project reflects a deep investment in the health and vitality of the region and is part of ChristianaCare’s larger plan, announced in July, to invest more than $865 million in Delaware over the next three years.
The 87,000-square-foot Health Center will rise at 621 Middletown Odessa Road, next to ChristianaCare’s existing freestanding emergency department. Designed as a modern, multidisciplinary hub, the facility will expand access to comprehensive services and create more than 70 new full-time jobs, boosting both community health and the local economy.
“Today we take an exciting step forward for Delaware, as part of ChristianaCare’s $865 million investment to expand access and strengthen health across our state,” said Janice E. Nevin, M.D., MPH, President and CEO of ChristianaCare. “This new health center is a promise to Delawareans: that they will have access to exceptional care close to home, delivered with love and excellence. More than a building, it represents our vision for healthier communities, our deep commitment to those we serve, and a future where every neighbor can thrive.”
A Holistic, Patient-Centered Experience The ChristianaCare Health Center at Middletown will bring together a wide range of services in one convenient location, including:
Primary and specialty care. Women’s health, behavioral health, oncology, cardiovascular care, pediatrics, neurology, imaging, diagnostics and lab testing. Hybrid exam rooms with interactive digital tools that allow family members to join virtually. Calming waiting areas with sensory-sensitive design features, plus friendly floor ambassadors to help patients navigate the building. Healing environments that include walking trails and abundant natural light. “We are designing care around people, not around appointments or buildings,” said Pauline Corso, president of Ambulatory Network Continuity and Growth at ChristianaCare. “From easy parking to advanced care coordination, every detail of this new center is aimed at making health care more welcoming, more connected and more human.”
A Community Partnership ChristianaCare has been part of the Middletown community since 2009, when it first acquired the land that is now home to the freestanding emergency department. Last year, that facility provided care for more than 32,000 patient visits.
“This groundbreaking is a proud moment for our town,” said Ken Branner, mayor of Middletown. “ChristianaCare has been a trusted partner for many years, and this new facility shows a lasting commitment to our residents. It will bring top-quality care closer to home and create good jobs right here in our community.”
