A New Approach in Cancer Medicine: Development of a Novel “Degraders” for the Selective Elimination of Cancer Cells
Researchers from two Technion faculties have jointly developed a new compound and demonstrated its effectiveness against aggressive tumor cells
A study published in Oncogene presents an innovative strategy for the particularly complex medical challenge of destroying aggressive, treatment-resistant tumors.
The research was jointly led by early-career scientists Dr. Avital Oknin Vaisman and Dr. Deepanjan Panda from the laboratories of Prof. Amir Orian, head of the Rappaport Center for Cancer Research at the Technion-Israel Institute of Technology, and a faculty member in the Ruth and Bruce Rappaport Faculty of Medicine, and Prof. Ashraf Brik of the Schulich Faculty of Chemistry.
Aggressive cancers such as bone tumors (sarcomas) and melanoma that do not respond to molecular therapies have very limited treatment options, making them a significant unmet need in oncology. These cancer cells depend heavily on proteins called oncoproteins and have evolved ways to avoid programmed cell death. Because of this, therapies that both target oncoproteins and trigger programmed cell death may offer a promising strategy for effectively treating these cancers.
The researchers developed a new class of molecules called R4VPs, belonging to a novel group of compounds known as PROTACs (PROtein TArgeting Chimeras/Degraders. Unlike conventional inhibitors, which block the activity of proteins, PROTACs induce the degradation of target proteins through the ubiquitin pathway. This represents a pioneering approach for targeting molecular drivers of cancer.
The Technion researchers are the first to develop a dual-targeting PROTAC that simultaneously degrades the enzyme RNF4, which is essential for the stability of oncoproteins, and VHL, an enzyme that prevents a form of programmed cell death known as ferroptosis. Exposure to these compounds kills cancer cells within just a few hours.
In their study the researchers demonstrate that this intervention is particularly effective against cancer cells that have developed resistance to existing therapies, as well as against various types of bone cancer cells isolated directly from patients’ tumors during surgery. Moreover, the compounds exhibit remarkable selectivity: they target almost exclusively cancer cells while sparing healthy cells, thereby avoiding the side effects commonly associated with chemotherapy and other standard anticancer treatments.
This novel strategy for the selective targeting of cancer cells and opens the door to the development of a new generation of precision medicines capable of overcoming resistance to existing therapies and improving survival rates for patients with aggressive cancers. However, the researchers emphasize that further studies in mouse models and clinical trials in humans are now required to evaluate safety and efficacy before the new approach can be applied in medical practice.
The study also involved the research groups of Prof. Markus Diefenbacher of the Helmholtz Munich Research Center and Prof. Torsten Mosler of Goethe University Frankfurt.
The research was supported by the Israel Innovation Authority (KAMIN Grant), the Rappaport Institute for Research in the Medical Sciences at the Technion, the Flinkman Family Cancer Research Fund, the Israel Cancer Research Fund (ICRF), and the German-Israeli Project Cooperation Foundation (DIP).
Photos: • Prof. Amir Orian • Prof. Ashraf Brik • Dr. Avital Oknin Vaisman • Dr. Deepanjan Panda
Oncogene
Experimental study
Cells
Discovery of ferroptosis-inducing R4VP compounds for targeting aggressive cancers
5-Jun-2026