Cancer

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The National Institute for Biotechnology
in the Negev Ltd.
Ben-Gurion University of the Negev

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The Rotblat laboratory examines the molecular biology of cancer from the perspective of lncRNA and protein translation. Specifically, they are interested in cancers of the brain, with a particular focus on childhood cancer. Rotblat and his team look to delineate the role of lncRNAs in cancer cells, given how lncRNAs govern or are involved in the regulation of a long list of cellular events.

Healthy and cancerous tissues can be distinguished by stresses within and unique to a tumor. For example, although cancerous cells can create their own blood vessels, tumors experience an inconstant supply of oxygen, glucose and nutrients. Yet, despite receiving pulses, rather than a steady flow of these components, tumor cells survive. For this, cancer cells reprogram their transcriptome, proteome, and metabolism to adapt to the stressful environment that exists within a solid tumor. As such, we can target the processes that allow tumor cells to adapt to starvation conditions as a therapeutic strategy.

In adapting to nutrient deprivation and a variety of stresses, cells reduce global protein synthesis – an energetically demanding and tightly regulated process – while promoting the synthesis of specific proteins. Certain proteins have thus evolved to regulate protein synthesis and to sense and respond to metabolic stress. Dr. Rotblat’s team has found that cancer cells upregulate the expression and activity of a negative regulator of mRNA translation, events which support the adaptation of these cells to nutrient deprivation. These findings led Dr. Rotblat and his group to postulate that endogenous negative regulators of mRNA translation support adaptation processes that occur inside the tumor, making them promising drug targets. One such negative regulator inhibits an oncogenic protein that is considered an inhibitor of oncogenesis. However, the same regulator has also been shown to play a critical role in tolerance to nutrient deprivation and in promoting the translation of specific transcripts that allow for tumor cell survival in the face of hypoxia. These findings suggest that tumor cells exploit this negative regulator to adapt to nutrient deprivation. Having identified a new target in the fight against cancer, the Rotblat laboratory now hopes to develop small molecules that block tumor cell adaptation to glucose starvation for use as potential anti-cancer drugs.

Dr. Barak Rotblat

Dr. Rotblat studies the molecular biology of cancer by examining the role of long non-coding RNAs and regulators of mRNA translation. Among other functions, long non-coding RNAs (lncRNA) control regulation in cells. Protein content analysis shows that a cancerous cell is very similar to a normal cell from the same tissue; for example, a cancerous breast cell is more similar to a breast cell than to a cancerous cell in the lung. However, while the protein profiles of healthy and cancerous cells from a given tissue are very similar, their lncRNA content is very different. Therefore, lncRNA represents a promising drug and therapeutic target. Regulating mRNA translation is key in the cellular mechanism by which tumor cells adapt to stress. Dr. Rotblat and his colleagues seek drug targets and inhibitor molecules aimed at processes that are used by cancer cells to adapt to starvation conditions, such as found in a tumor.

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