Bar-Ilan study may provide a response for types of hematologic cancers currently considered untreatable.
Israeli researchers at Bar-Ilan University have developed a novel treatment approach in the fight against hematologic cancers that involves attacking the cytoskeletal protein, called WASp, which has a unique structural condition in active hematologic cancer cells while leaving healthy cells unharmed.
Cancer cells depend on actin, a protein that plays a key role in the cytoskeleton, to carry out their malignant functions. Malignant cells need actin to be active, proliferate, migrate and invade. The WASp protein controls actin’s activity and structure.
The Bar-Ilan team focused on destroying WASp in malignant cells and demonstrated that the degradation of WASp assists in inhibiting and destroying these malignant cells.
To date, the involvement of WASp in cancer has not been completely understood, but it is known to be found in cancer cells in a unique structure that allows it to be identified and manipulated. Inducing the degradation of WASp can destroy mainly malignant cells without threatening healthy cells, and can even be used to treat most types of hematologic cancers.
Focusing on the damage of the cytoskeleton of the malignant cell, the research team performed screening to identify SMCs (small molecule compounds) that degrade the WASp compound. The team used bio convergence technologies to identify the SMCs, which combine biology with various engineering technologies, including artificial intelligence and machine learning.
By using a device developed by Prof. Yanai Ofran of Bar-Ilan, small molecules were identified in Prof. Mira Barda-Saad’s lab that damage cancer cells without posing too much risk to healthy cells.
The researchers proved the efficacy of using SMCs to inhibit proliferation and destroy the malignant cells in laboratory experiments using cells taken from actual patients, as well as a mouse model carrying human blood cancer.
The WASp protein interacts with another protein, WIP, which binds to a specific point known as the “recognition site” and protects it against degradation. The SMCs bind to the recognition site and prevent the two proteins from binding together, thereby promoting degradation of the WASp, which is no longer protected by WIP.
This study may provide a response for types of hematologic cancers for which treatment has not yet been found. The focused targeting of WASp, which aims to damage the cytoskeleton of the blood cancer cells, could replace treatments such as chemotherapy and other biological therapies which, because of their non-specificity, damage not only cancer cells but other cells in the body, or cause cancer cells to become resistant to treatment.
Prof. Barda-Saad notes that SMCs are already being used for various medical purposes, and they can be administered to patients through the blood system or by ingestion.