Cancer’s aggressiveness is often linked to the abnormal behavior of genes known as oncogenes. While mutation is a well-known driver of cancer, it’s not the only mechanism. Sometimes, a cell accumulates a dramatically increased number of copies of an oncogene – dozens, even hundreds. This amplification of oncogenes occurs in a significant proportion of solid tumors and can contribute to more aggressive disease, making it harder for the body’s defenses to detect and increasing resistance to treatment.
Now, researchers are exploring a new strategy: turning this very amplification into a weakness that cancer cells can’t overcome. A study led by Drs. Sandra Rodríguez-Perales and Raúl Torres, from the Spanish National Cancer Centre (CNIO) and the CIEMAT, respectively, demonstrates a potential approach to exploit oncogene amplification as a therapeutic target.
The research, published in Molecular Cancer in December 2025, presents a proof-of-concept in animal models for destroying tumor cells containing amplified oncogenes through genome editing. The core idea is to convert the sheer excess of oncogene copies into an “Achilles’ heel” for the cancer.
“We used the CRISPR-Cas9 gene editing tool to make a cut within the amplified oncogene,” explains Dr. Rodríguez-Perales. “Normally, when a cell detects damage to its DNA, it repairs it. But if the gene is amplified – existing in multiple copies – the cut occurs in all of them, leading to a high level of genetic damage. Unable to fully repair this extensive damage, the cell activates its programmed cell death machinery.”
While gene editing can potentially affect healthy cells, the researchers found that these cells, lacking the amplified gene, are able to repair the induced cuts. “This addresses one of the major bottlenecks in gene therapy: achieving selective cutting, targeting tumor cells – in this case, those with the amplified oncogene – without harming healthy cells,” the authors state.
The strategy was tested in cellular and animal models of neuroblastoma, small-cell lung cancer, and colorectal cancer. Experiments showed a reduction in tumor growth, increased animal survival, and changes suggesting an anti-tumor immune response.
The induced cell death is thought to trigger an immune response. The team hypothesizes that this type of cell death can alert immune cells and promote activation of an anti-tumor response. They have already detected initial signs of this activation in their experiments and plan to investigate this further.
“Genome editing of amplification in tumors may provide a basis for developing precision gene therapies for cancers that are resistant to treatment,” the scientists suggest.
They have also begun exploring combinations with existing therapies in animal models. Combining gene editing with a standard chemotherapy drug for neuroblastoma resulted in a greater number of cell deaths than either treatment alone.
Alejandro Nieto and Marta Martínez-Lage, co-first authors of the study, affirm that “the study demonstrates a novel CRISPR-based strategy that converts oncogene amplification into a vulnerability, triggering death only in tumor cells, which could open a pathway to precision therapies for difficult-to-treat tumors.”
This research was supported by public funding from the Spanish National Research and Innovation Plan, the Carlos III Health Institute, and FEDER funds, as well as private funding from the Spanish Association Against Cancer (AECC).
New Approaches to Glioblastoma Treatment
In related research, scientists at the University Autonomous of Barcelona (UAB) are exploring a novel approach to treating glioblastoma, the most aggressive type of brain tumor. Their work, published in Advanced Science, focuses on bioadhesive patches designed to deliver a localized, controlled dose of oxidative stress to tumor cells, minimizing systemic side effects.
Glioblastoma is a particularly challenging cancer to treat, with recurrences common even after aggressive surgery, radiation, and chemotherapy. The UAB team’s patches are intended to be placed at the site of tumor removal during surgery to eliminate any remaining cancer cells.
Combination Therapy for Prostate Cancer
Johnson & Johnson has announced that the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the indication of AKEEGA® (niraparib and abiraterone acetate in a single tablet) to include treatment for patients with metastatic castration-resistant prostate cancer (mCRPC) with BRCA1/2 mutations. The recommendation covers the combination of niraparib and abiraterone acetate with prednisone or prednisolone in patients with these mutations.
These developments highlight the ongoing efforts to refine cancer treatment strategies, moving towards more targeted and personalized approaches. The research into exploiting oncogene amplification, in particular, represents a promising avenue for addressing cancers that have become resistant to conventional therapies.
