Israeli researchers at the Technion have developed a new class of experimental molecules designed to selectively destroy aggressive cancer cells, including cells that have become resistant to existing treatments.
The research focuses particularly on difficult-to-treat cancers such as sarcomas and melanoma. The findings were published in Oncogene.
The study was conducted by researchers from the Technion's Rappaport Faculty of Medicine and Schulich Faculty of Chemistry, in the laboratories of Prof. Amir Orian and Prof. Ashraf Brik.
Many modern targeted cancer drugs work by blocking a protein that tumor cells need in order to survive.
But cancer cells can adapt. Mutations and alternative biological pathways may eventually allow the tumor to continue growing despite treatment.
The Technion team explored another strategy: instead of simply blocking an important cancer protein, make the cancer cell destroy it altogether.
How Protein Degraders Work
The researchers developed molecules known as R4VPs, belonging to a family of compounds called PROTACs — PROteolysis TArgeting Chimeras.
PROTACs use the cell's own protein-disposal machinery to eliminate selected proteins.
The Israeli team developed a dual-targeting PROTAC that acts on two proteins: RNF4, involved in maintaining cancer-driving proteins, and VHL, which is connected to the regulation of a form of programmed cell death called ferroptosis.
By targeting both mechanisms simultaneously, researchers were able to trigger rapid death of cancer cells.
In laboratory experiments, the compounds demonstrated activity against cancer cells resistant to existing therapies and against several types of bone cancer cells obtained directly from patients' tumors during surgery.
The researchers also reported a high degree of selectivity for cancer cells compared with healthy cells.
That selectivity is particularly important because one of the central goals of precision oncology is to attack cancer while minimizing damage to healthy tissue.
However, these compounds are not yet an available treatment. Further studies in animal models are required, followed by clinical trials in humans, before researchers can determine whether the approach is safe and effective for patients.
If you have been diagnosed with an aggressive or treatment-resistant cancer and would like your case reviewed by Israeli specialists, contact Sapir Medical Clinic. We can help arrange a second medical opinion, specialist consultation, diagnostic review, and treatment in Israel.