the scientist The internal structure of a key protein involved in colorectal cancer has been revealed, paving the way for new drugs to treat this disease.
The tankyrase protein is involved in a wide range of processes within cells, researchers suggest, and this could lead to better and less toxic anticancer agents.
Using Nobel Prize-winning technology, scientists have discovered how proteins turn on and off by self-assembling into 3D chain-like structures.
An elusive key protein plays a particularly important role in helping intestinal cancer progression.
cancer research scientist, London (ICR) believes their work will open the door to new types of cancer treatments in which tankyrase can be controlled more precisely and with fewer side effects.
Professor Sebastian Guettler, Deputy Director of Structural Biology at ICR, who led the study, said: escaped our understanding.
“We’re catching up. We have all these drugs to block the production of tankyrase, but we don’t have enough basic understanding to use them as a treatment.
“We have shown how tankyrase is switched on and changes from a ‘lazy’ enzyme to an active enzyme.
“If we can create less toxic drugs to control this process, it could pave the way for effective colorectal cancer treatments in the future.”
According to a survey published in NatureThis fundamental discovery may have implications for the treatment of various cancers, as well as diabetes, inflammatory diseases, heart disease and neurodegenerative diseases.
ICR Chief Executive Professor Kristian Helin said:
“Almost all colorectal cancers have hyperactive Wnt signaling that acts through tankyrase and could potentially be treated with agents that target it.
“We hope that these important advances in our understanding of tankyrase will help overcome the limitations of currently available drug candidates and bring us one step closer to new targeted bowel cancer treatments.
“This study may have broad implications, as tankyrase is also involved in regulating a wide range of processes not only related to cancer but also to various diseases.”
Over the past decade, scientists have developed drugs that inhibit tankyrase to treat bowel cancer.
To truly understand how tankyrase inhibitors work and how to develop less toxic treatments, ICR scientists set out to discover new structural information using state-of-the-art cryo-electron microscopy. I was.
This very powerful type of microscope freezes samples at -180°C, allowing fine details of protein shape to be imaged.
This allowed us to visualize and understand how tankyrase “self-assembles” into fibers (chain-like structures) and why fiber formation is required to activate tankyrase itself.
Researchers believe that allowing specific regions of proteins to assemble and disassemble into different structures is an exciting target for future anticancer drugs.
It is hoped that they will be able to design structurally distinct tankyrase inhibitors – safer and more effective, urgently needed to treat bowel cancer and other diseases in which tankyrase is associated. It is typical.
This study was primarily funded by Cancer Research UK, Wellcome, and ICR.
https://www.independent.co.uk/news/health/scientists-nobel-prize-london-nature-cancer-research-uk-b2231533.html New discoveries could lead to new drugs for bowel cancer, study suggests