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Sussex research indicates an effective new treatment for breast cancer

A five-year study, the relationship between structure and function of the carcinogenic compound LMTK3, advances the science, indicates that LMTK3 inhibitors can be used effectively to treat breast cancer and other types of cancer.

An international study led by scientists at the University of Sussex has provided strong evidence for an effective new target for treating breast cancer. The five-year study, called “Structure-Function Relationship in Tumor LMTK3”, will be published Science Advances, Researchers from seven institutions in three countries including Diamond Light Source in the United Kingdom participated. It is suggested that LMTK3 inhibitors can be used effectively to treat breast cancer and other types of cancer. The LMTK3 carcinogen (Lemur Tyrosine Kinase 3) structure defines its role and functions allowing drug inhibition as a novel treatment strategy.

It is hoped that the research will allow the development and improvement of LMTK3 inhibitors as a new type of oral anticancer drug for patients and have potential value not only for breast cancer patients but also for patients with lung, stomach, thyroid, and bladder cancer.

LMTK3 is a protein involved in the development and progression of various malignancies and other diseases (such as related central nervous system), which is not usually included in commercial kinase screening assays. The research successfully demonstrated that LMTK3 is an active kinase and actively reports a compound that binds to and inhibits this protein leading to anticancer effects in cells and in breast cancer models in mice.

“By resolving the crystal structure of LMTK3, we showed that it possesses all the hallmarks of an active protein kinase. LMTK3 plays a pivotal role in controlling cellular processes,” says Georgios Giamas, professor of cancer cell signaling at the University of Sussex, who led the research. It makes some cancer treatments (such as chemotherapy and endocrine treatments) less effective.

“We are now in the process of taking this research to the next stage by developing specific drugs for LMTK3. Hopefully in the next five years we will have clinical trials that are incredibly fast for this type of operation.”

It would be expected that the development of oral LMTK3 inhibitors might have a broad clinical benefit, either as monotherapy or as a combination therapy, for example with chemotherapy, immunotherapy or endocrine therapies. Thus, an LMTK3 inhibitor may be used in conjunction with complementary therapies to increase therapeutic efficacy and help overcome existing cancer therapy resistance mechanisms.

The researchers say the work is a great example of international scientific collaboration with several groups that have come together to help on a challenging project. In particular, OPPF (Oxford Protein Production Facility) and Synchrotron in the UK, Diamond Light Source has worked with groups to produce the protein of interest to them (LMTK3) and to help solve its crystal structure. “It is often difficult to obtain large-well diffraction crystals and LMTK3 was no exception. By close collaboration between OPPF and I24 and by exploiting a finely focused X-ray beam at I24 to collect wedges of data from multiple crystals, we were able to obtain the key diffraction data for the study, Robin Owen, Beamline Principal Scientist at MX beamline I24, commented in Diamond. This research project is also great evidence of the strong synergies between Diamond and neighboring research institutes such as the Harwell Research Complex that houses sample preparation.

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the paper: The structural and functional relationship of the carcinogen LMTK3 will be published in the journal Science Advances. November 13, 2020 – DOI: 10.1126 / sciadv.abc3099.

The Authors: a. Ditzio C. Cilibrasi; Milton Harris in. T Jagliano, MC Yacini T. Simon Brodromo; Giamas; University of Sussex N. Simigdala; P. Netafilo; a. Clinics

The Biomedical Research Foundation of the Academy of Athens A. Papakyriakou National Center for Scientific Research “Demokritos” JE Nettleship; RJ Owens University of Oxford JE Nettleship; RG Owens Research Complex at Harwell; JH Lu; S. Soni; Simbatian H.-J. Lenz University of Southern California; s. Khorshid; B. Carter; NE Chayen; Stepping Imperial College; L. Chu; s. Hassel Hart Pearl LH SM Rowe University c. Spencer in Sussex. RL Owen – Diamond Light Source; RJ Owens – Rosalind Franklin Institute; T. Gagliano – University of Udine

For more media information: Please contact Diamond Communications: Lorna Campbell +44 7836 625999 or Isabelle Boscaro-Clarke +44 1235 778130

About diamond light source: http: // www.Diamond.a.United kingdom

Diamond Light Source is the UK’s national synchrotron, providing the industrial and academic user communities with access to the latest analytical tools to enable science that changes the world. In the form of a huge ring, acting like a giant microscope, it accelerates electrons to speeds close to light, to produce light 10 billion times brighter than the sun, which is then directed to 33 labs known as “ray lines” In addition, Diamond provides Access to several integrated laboratories including the Electronic Bio-Imaging Center (eBIC) and the Electronic Physical Sciences Imaging Center (ePSIC).

Diamond acts as an agent of change, tackling 21st century challenges such as disease, clean energy, food security, and more. Since the start of operations, more than 14,000 researchers from academia and industry have used diamonds to conduct the experiments, supported by nearly 700 world-class employees. More than 9000 scientific articles published by our users and scholars.

Funded by the UK government through the Science and Technology Facilities Council (STFC), and through the Wellcome Trust, Diamond is one of the most advanced scientific facilities in the world, and its pioneering capabilities help keep the UK at the forefront of science institutions. Research.

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