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New target for potential blood cancer treatment

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Mutations present in a blood cancer known as follicular lymphoma have revealed new molecular targets for potential treatments, according to researchers at Queen Mary University of London (QMUL) together with collaborators at the Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology.

Follicular lymphoma is a common type of blood cancer and one of the most common non-Hodgkin lymphomas, with more than 2,500 people diagnosed in the UK every year. Whilst the condition is normally responsive to existing therapies, the cancer often returns frequently and eventually develops resistance and, for some, their cancer becomes more aggressive and difficult to treat.

Dr Jessica Okosun from QMUL's Barts Cancer Institute said: "One of the mutations that we have identified allows follicular lymphoma tumours to turn on growth signals regardless of whether nutrients are available, thereby evading normal restrictions on its growth.

"Remarkably, the mutations we have discovered have not been seen in other cancer types. However, drugs that directly target this nutrient-sensing mechanism are currently used to treat other types of cancer, and may benefit patients with follicular lymphoma."

The research, published in Nature Genetics, identified mutations in several components of the body's nutrient sensing pathway, called mTOR, occurring in 30% of follicular lymphoma patients. This pathway is switched on when there is sufficient 'food' available for a cell to grow and survive. While more research is needed, the team have shown that mutations in one of the genes called RRAGC is central to keeping this growth signal on regardless of the nutrient conditions.

Inhibitors that directly target the MTOR pathway are currently used to treat other types of cancer. The researchers say these drugs may benefit patients with follicular lymphoma, particularly those who harbour mutations in that pathway, and may allow them to select subsets of patients that they believe may respond best to these therapies.

The original mTOR inhibitor called rapamycin was discovered in the 1960s in the soils of Easter Island, when it was found to be an effective anti-fungal agent. Newer mTOR inhibitors have more recently been shown to be able treat some forms of cancer, and could be a candidate for further testing against follicular lymphoma.

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The study was funded by Cancer Research UK and the Kay Kendall Leukaemia Fund.

Notes to editors

Recurrent mTORC1-activating RRAGC mutations in follicular lymphoma

Jessica Okosun et al

Nature Genetics 2015

DOI: 10.1038/ng.3473

About Queen Mary University of London

Queen Mary University of London (QMUL) is one of the UK's leading universities, and one of the largest institutions in the University of London, with 20,260 students from more than 150 countries.

A member of the Russell Group, we work across the humanities and social sciences, medicine and dentistry, and science and engineering, with inspirational teaching directly informed by our research – in the most recent national assessment of the quality of research, we were placed ninth in the UK (REF 2014).

We also offer something no other university can: a stunning self-contained residential campus in London's East End. As well as our home at Mile End, we have campuses at Whitechapel, Charterhouse Square and West Smithfield dedicated to the study of medicine, and a base for legal studies at Lincoln's Inn Fields.

We have a rich history in London with roots in Europe's first public hospital, St Barts; England's first medical school, The London; one of the first colleges to provide higher education to women, Westfield College; and the Victorian philanthropic project, the People's Palace based at Mile End.

QMUL has an annual turnover of £350m, a research income worth £100m, and generates employment and output worth £700m to the UK economy each year.

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