The fight is on: Israeli scientists reveal new approach for treating blood cancers
New method, developed by researchers from Bar-Ilan University, uses combination of biology, AI tech and machine learning; Can destroy malignant cells “without threatening healthy cells”
By ILANIT CHERNICK
Researchers at Israel’s Bar-Ilan University have found a new approach to treating blood cancers using a combination of biology, AI tech and machine learning.
According to the university, the new method “involves attacking the cytoskeletal protein, called WASp, which has a unique structural condition in active hematologic cancer cells.”
Developed by Prof. Mira Barda-Saad and her research team from the Mina and Everard Goodman Faculty of Life Sciences, she explained that the role of WASp in cancer is not yet completely understood, “but it is known to be found in cancer cells in a unique “open” structure that allows it to be identified and manipulated.”
“In order to carry out their malignant functions, cancer cells depend on actin, a protein that plays a key role in the cytoskeleton,” Barda-Saad said. “Malignant cells need actin to be active, proliferate, migrate and invade.”
The team stressed that “the WASp protein actually controls the actin’s activity and structure, and through their research, they aimed to destroy WASp in malignant cells,” demonstrating that the breakdown of WASp plays a key role in destroying malignant cells.
Even more importantly, their method of breaking down what’s called “open” WASp can destroy malignant cells “without threatening healthy cells,” and can even be used to treat most types of blood cancers.
This study, which has been underway since 2015, could help in fighting several types of hematologic cancers that don’t yet have treatments. This treatment method, which targets the WASp protein, could replace treatments such as chemotherapy and other biological therapies because it only targets unhealthy malignant cells and doesn’t damage healthy cells.
Because of their non-specificity, treatments like chemo and biological therapies damage not only cancer cells but also other cells in the body, and sometimes even cause cancer cells to become resistant to treatment.
Discussing how their method works, Barda-Saad said the team performed screening to identify “small molecule compounds (SMCs) 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,” she said.
Using a special device developed by Prof. Yanai Ofran of Bar-Ilan, the small molecules that were identified by the team were found to damage cancer cells without posing too much risk to healthy cells.
In conjunction with Sheba Medical Center at Tel HaShomer, the researchers used malignant cells from cancer patients and did further lab testing, successfully proving that by using SMCs they could slow down proliferation and destroy these malignant cells. Similar testing was also done in a mouse model carrying human blood cancer.
According to the researchers, “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 then 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.”
Highlighting what led to this novel approach, Barda-Saad said that “the idea arose in my lab when we discovered the process of WASp protection during a study that was published in 2014… This primary research led to the development of a new treatment strategy.”
Using prior information of WASp degradation sites, which were also identified in Prof. Barda-Saad’s lab, gave the researchers the ability “to define the various properties of the binding sites and allowed them to predict the types of SMCs that would bind to the interphase between the WASp and WIP proteins, and separate them.”
The research team also used machine learning to predict how the WASp protein would interact with its environment “and to identify molecules that would not block the WASp degradation sites.”
Prof. Barda-Saad made it clear that SMCs “are already being used for various medical purposes, and they can be administered to patients through the blood system or by ingestion.” She pointed out that “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,” Barda Saad stressed. “Nonetheless, the concept must understandably undergo pre-clinical and clinical safety trials, as is standard procedure with any drug.”
She added that the research focused 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.”
For Prof. Barda-Saad, the development of this new therapeutic strategy is more than just a scientific achievement. “For many years… I concentrated on basic research [but] 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 questioned.
And although “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,” she is determined to use her vast knowledge to continue her research in the fight against blood cancers.
The team’s research was recently published in the journal Nature Communications and was conducted with funding from the Israel Innovation Authority.
**Featured Image: Israeli professor, Prof. Mira Barda-Saad of the Mina and Everard Goodman Faculty of Life Sciences, who led the study. (Photo Credit: Bar-Ilan University)