[Nature Sub-Journal] A new method for treating leukemia!

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Author: Ashley Guide: In 2018, hematological malignancies accounted for about 10% of all cancer-related deaths.
Among them, non-Hodgkin's lymphoma and leukemia are the main hematological cancers
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At present, its treatment is still based on chemotherapy and radiotherapy, and it is accompanied by serious side effects
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Recently, researchers at Bar-Ilan University in Israel revealed a new type of treatment against blood cancers
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Researchers at Bar-Ilan University in Israel have revealed a new treatment method against blood cancers developed by Professor Mira Barda-Saad of Mina and Everard Goodman School of Life Sciences and his research team, which involves attacking the cytoskeleton The protein WASp, which has a unique structure in active blood cancer cells
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In order to perform its malignant function, cancer cells rely on actin, a protein that plays a key role in the cytoskeleton
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Malignant cells require actin activity, proliferation, migration and invasion
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The WASp protein controls the activity and structure of actin
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The Bar-Ilan team focused on destroying WASp in malignant cells and proved that the degradation of WASp helps to inhibit and destroy these malignant cells
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Their research was recently published in the journal Nature Communications, entitled "Targeting the actin nucleation promoting factor WASp provides a therapeutic approach for hematopoietic malignancies"
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So far, the involvement of WASp in cancer is not fully understood, but it is known that it has been found in cancer cells with a unique "open" structure, which can be identified and manipulated
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Inducing the degradation of "open" WASp can destroy the main malignant cells without threatening healthy cells, and can even be used to treat most types of blood system cancers
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In order to destroy the cytoskeleton of malignant cells, the research team conducted a screen to identify SMCs (small molecule compounds) that degrade WASp compounds under their "open" structural conditions
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In order to identify small molecule compounds, they used biopolymerization technology, which combines biology with various engineering techniques, in this case artificial intelligence and machine learning
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By using the equipment developed by Professor Yanai Ofran of Bar-Ilan, in Professor Barda-Saad's laboratory, small molecules were identified, which can actually damage cancer cells without causing too much harm to healthy cells
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In laboratory experiments, the researchers used cells taken from actual patients, cooperated with the Sheba Hospital in Israel and a mouse model carrying human blood cancer, and demonstrated the efficacy of using small molecule compounds to inhibit proliferation and destroy malignant cells
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The WASp protein interacts with another protein, WIP, which binds to a specific point called a "recognition site" to protect it from degradation
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The small molecule compound binds to the recognition site and prevents the two proteins from binding together, thereby promoting the degradation of WASp, while WIP no longer protects WASp
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Professor Barda-Saad said: "When we discovered the WASp protection process in a study published in Science Signaling in 2014, my laboratory came up with this idea
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This preliminary study prompted the development of a New treatment strategies
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"This research has been carried out with funding from the Israel Innovation Agency since 2015, and may provide a relief for treating undiscovered types of blood system cancers
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The main target of WASp is to destroy the cytoskeleton of blood cancer cells.
It can replace therapies (such as chemotherapy) and other biological treatments.
Due to its non-specificity, it not only destroys cancer cells, but also destroys other cells in the body, or causes cancer cells to become resistant to treatment.
Medicinal properties
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The prior knowledge of WASp degradation sites was also identified in Professor Barda-Saad’s laboratory, allowing researchers to define the various properties of the binding sites and enabling them to predict small molecules that bind to WASp and WIP proteins.
Type of compound and separate it
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The research team used machine learning to predict the interaction of WASp with its environment and determined molecules that would not block the degradation site of WASp
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Once these molecules are discovered, the researchers will use cell culture molecular and biochemical experiments to verify their activity, and then use a mouse model that carries human blood cancer
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Professor Barda-Saad pointed out that small molecule compounds have been used for various medical purposes, which can be administered to patients through the blood system or through ingestion
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One indicator of the safety of this new treatment strategy is the structure of WASp in normal blood cells: Compared with the open structure found in malignant blood cells, it is a "closed" structure that prevents small molecule compounds from binding to the recognition site
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Therefore, in theory, the use of small molecule compounds will not cause any major risks
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Nevertheless, just like the standard procedure of any drug, the concept must undergo preclinical and clinical safety trials, which is understandable
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This research is mainly focused on non-Hodgkin's lymphoma, but since other types of blood cancers also express target proteins (target proteins are not expressed in cells other than blood cells), it is likely to be effective as well
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For Professor Barda-Saad, developing this new treatment strategy is not just a scientific achievement
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She said: "During my doctoral and postdoctoral research at the Weizmann Institute, and later at the National Institutes of Health (NIH) in Maryland, USA, I conducted many years of basic research
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Discovered in my family Several cancer cases in, led me to take an applied approach-how do I use basic knowledge and use it to formulate treatment strategies
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The process is very lengthy because it requires an in-depth understanding of how cells work and how cancer cells are different from normal cells What are their weaknesses that can be exploited? In this research, we used a lot of knowledge we acquired to design an applicable strategy
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"Reference: https://medicalxpress.
com/news/2021-10 -approach-leukemia.
html Note: This article aims to introduce the progress of medical research and cannot be used as a reference for treatment options
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If you need health guidance, please go to a regular hospital
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