ChristianaCare researchers have made a major advance in treating one of cancer's toughest challenges: drug resistance. Using CRISPR gene editing, the team successfully disabled the gene that helps cancer cells survive chemotherapy, making previously untreatable tumors vulnerable to standard treatments again.
Published in Molecular Therapy Oncology, the breakthrough offers new hope to patients with head and neck cancer — the seventh most common cancer worldwide, with cases expected to rise by 30% annually by 2030. Many patients eventually reach a point where chemotherapy simply stops working.
Targeting the Master Switch
The researchers focused on a gene called NRF2, which acts like a master switch that helps cancer cells survive stress and resist chemotherapy. Rather than targeting a single protein (as traditional drugs do), the team chose to develop a genetic therapy that disables the gene itself through CRISPR gene editing.
This work builds on earlier studies in lung cancer, where blocking NRF2 made tumors more responsive to chemotherapy and improved survival in animal models.
Precision Matters: Location, Location, Location
The study revealed something crucial: where you cut the gene matters. The strongest results came from targeting exon 4, a part of the gene that controls a key section of the NRF2 protein. Editing this region achieved the 90% reduction, while targeting exon 2 was less effective despite high levels of gene disruption.
The team also discovered that "exon skipping" — where sections of genetic code are rearranged — can affect outcomes. This highlights the importance of careful design and testing when building gene-editing therapies.
Beyond One Cancer Type
The approach worked in both head and neck cancer cells AND esophageal cancer cells, suggesting it could help treat many solid tumors with high NRF2 levels and strong drug resistance.
What Comes Next
The team is now focused on finding the safest and most effective way to deliver the gene-editing tools directly to tumors. The goal: reduce how much standard treatment a patient needs while achieving better results with fewer side effects.
"Drug resistance is one of the biggest challenges in cancer care," said Dr. Rivera‑Torres. "If we can overcome it with gene editing, we could give patients more time, better quality of life and a renewed sense of hope."
Source: ChristianaCare Gene Editing Institute, published in Molecular Therapy Oncology
