Israeli scientists have achieved a significant breakthrough in cancer treatment using CRISPR gene-editing technology, successfully eliminating 50% of head and neck tumors in model animals by targeting a single gene. This groundbreaking research, conducted at Tel Aviv University, challenges the long-held belief that CRISPR would be ineffective against cancer due to tumors' reliance on multiple genetic mutations.
The study, recently published in the peer-reviewed journal Advanced Science, was led by Dr. Razan Masarwy under the guidance of Prof. Dan Peer, Director of the university's Laboratory of Precision Nanomedicine and a global pioneer in mRNA-based therapeutics.
Targeting the Essential SOX2 Gene
The research team focused on the cancer-specific SOX2 gene, which is overexpressed in head and neck tumors and several other cancer types. "Our aim was to use genetic editing of a single gene expressed in this type of cancer to collapse the entire pyramid of the cancerous cell," explained Prof. Peer.
This approach contradicts conventional wisdom in cancer research, which suggested that eliminating a single gene would be insufficient to destroy cancer cells since they typically rely on multiple genetic alterations and can compensate when one pathway is blocked.
"Generally, CRISPR isn't used for cancer because the assumption is that knocking out one gene wouldn't collapse the whole pyramid," noted Prof. Peer. "In this study, we demonstrated that some genes are absolutely essential for cancer cell survival, making them excellent targets for CRISPR therapy."
Innovative Delivery System Overcomes Key Obstacles
A critical component of the study's success was the development of a precise delivery system to overcome one of the major challenges in applying CRISPR to cancer therapy. The researchers designed specialized lipid nanoparticles to carry the CRISPR system in an RNA format.
To ensure targeted delivery, they attached antibodies against the epidermal growth factor (EGF) receptor—a protein commonly expressed on these cancer cells—to the surface of the nanoparticles.
"These tumors are highly targeted," Prof. Peer explained. "Using our nano-lipid delivery system, we injected the drug directly into the tumor and successfully took out the gene—literally cutting it out from the cancer cell's DNA with the CRISPR 'scissors.'"
Remarkable Results in Model Animals
The treatment protocol involved three injections spaced one week apart. After 84 days, 50% of the tumors had completely disappeared—an effect not observed in the control group.
This achievement marks the first time CRISPR has been shown to completely eradicate tumors by targeting a single gene, potentially revolutionizing cancer treatment approaches.
Clinical Significance for Head and Neck Cancers
Head and neck cancers rank fifth in cancer-related mortality worldwide. These localized cancers typically begin in the tongue, throat, or neck before potentially metastasizing to other parts of the body.
Current treatment options primarily rely on surgery, radiation, and chemotherapy—approaches that often come with significant side effects and varying efficacy rates. This new CRISPR-based approach could potentially provide a more precise and less toxic alternative.
"If detected early, localized treatment can effectively target the tumor," said Prof. Peer, highlighting the potential clinical applications of their technique.
Building on Previous Breakthroughs
This isn't the first time Prof. Peer's team has made headlines with CRISPR technology. In 2020, they became the first researchers worldwide to use CRISPR to cut genes from cancer cells in mice in a cell-specific manner. The current study represents the first application of this approach to head and neck cancers.
Future Directions and Broader Applications
Encouraged by these promising results, the research team is already working to apply the same method to other cancer types, including myeloma, lymphoma, and liver cancer.
"Theoretically, this approach could be effective against many types of cancer cells," Prof. Peer stated. "Since cancer cells sometimes compensate with other genes, it's possible that additional genes need to be cut out, or perhaps not."
If this approach proves successful in human trials, it could transform cancer treatment by providing a more targeted alternative to conventional therapies, potentially reducing side effects while improving efficacy.
The study represents a significant step forward in precision medicine for cancer, demonstrating that with the right target and delivery system, CRISPR technology may indeed fulfill its promise as a revolutionary tool in the fight against cancer.
