Researchers at Bar-Ilan University have revealed a novel treatment strategy in the fight against hematologic cancers. The new approach involves attacking the cytoskeletal protein, called WASp, which has a unique structural condition in active hematologic cancer cells, without damaging healthy cells.
The research, which has been in the works since 2015 and was recently published in the journal Nature Communications, focuses on destroying WASp in malignant cells.
Much about the involvement of WASp in cancer remains unknown, but researchers have found an “open” structure, allowing them to identify and manipulate. Inducing the degradation of “open” WASp can destroy mainly malignant cells without threatening healthy cells, ultimately offering treatment for most types of hematologic cancers. Examples of hematologic cancer include leukemia, lymphoma, and multiple myeloma.
In order to damage the cytoskeleton of the malignant cell, the research team performed screening to identify SMCs (small molecule compounds) that degrade the WASp compound in its “open” structural condition. To identify the SMCs they used bio convergence technologies, which combine biology with various engineering technologies – in this case, artificial intelligence and machine learning (AI/ML), by using a device that originated at the university.
Prof. Mira Barda-Saad, who with her team developed the method, said that SMCs are already being used for various medical purposes, and they can be administered to patients through the blood system or by ingestion. One indicator of the safety of this new treatment strategy is the structure of WASp in normal blood cells: it is a “closed” structure, compared with the open structure found in malignant blood cells, which prevents the SMCs from binding to the recognition site. Therefore, theoretically speaking, using the SMCs does not pose any significant risk. Nonetheless, the concept must understandably undergo pre-clinical and clinical safety trials, as is standard procedure with any drug.
This research focuses primarily on non-Hodgkin’s lymphoma, but since other types of hematologic cancers also express the target protein, which is not expressed in cells that are not blood cells, there is a good chance that this can work for them, as well.
Prof. Barda-Saad noted that the development of this new therapeutic strategy is more than just a scientific achievement. “For many years during my doctoral and post-doctoral studies at the Weizmann Institute, and later on with the NIH in Maryland in the US, I concentrated on basic research. Several cases of cancer discovered in my family caused me to adopt an applicative approach – how could I take the primary knowledge and use it to develop a therapeutic strategy,” she said. “The process is lengthy and drawn out because it demands a deep understanding of how cells work and how cancer cells are different from normal cells – what are their weak points that can be exploited? In this research we used the vast knowledge we acquired in order to design an applicative strategy.”