Cancer therapy may be too targeted

Genetic landscape of rare cancer acts as a guide for future clinical trials

2014-03-16

(Press-News.org) Researchers have identified two novel cancer genes that are associated with the development of a rare, highly aggressive, cancer of blood vessels. These genes may now act as markers for future treatments and explain why narrowly targeted therapies that are directed at just one target fail.

Angiosarcoma is a rare cancer of blood vessels. It occurs either spontaneously or can appear after radiotherapy treatment. Although quite rare, with approximately 100 people diagnosed with the cancer in the UK each year, the survival outcomes for the cancer are poorer than many other cancer types.

Scientists have previously developed drugs against angiosarcoma that target specific cellular pathways involved in the formation of blood vessels. However, these drugs have had little or no success.

In this study, the team found that 40 per cent of angiosarcomas carry mutations in genes that control blood vessel growth, including two novel cancer genes, PTPRB and PLCG1.

"Because this cancer doesn't respond well to traditional chemotherapy and radiotherapy, it makes sense to develop drugs that target pathways that control blood vessel formation," says Dr Peter Campbell, co-lead author from the Wellcome Trust Sanger Institute "We found two novel cancer genes that control blood vessel formation which are mutated in this cancer and which could be targeted for treatment of this highly aggressive cancer."

However, in some patients, the team found multiple mutations in the pathway that controls blood vessel growth. These multiple mutations may make drugs developed for a single target ineffective in some patients. This study emphasises the need to take into account the effects multiple, co-operating mutations can have when designing targeted treatments for patients.

"This indicates that we may need to think more broadly to find a suitable treatment," adds Dr Campbell.

"This study really highlights the power that a limited number of samples can have to influence the clinical and biological understanding of a rare disease, in this case angiosarcoma," says Professor Adrian Harris, co-lead author from the University of Oxford. "Not only does our study change the way people view the biology of this tumour, it acts as a guide for future drug trials in angiosarcoma patients."

Because so few people are affected by angiosarcoma, clinical trials can be very difficult to conduct. With this new information researchers now need to determine if existing drugs could be effective against this detrimental cancer.

"It's extremely important to that we continue to study rare cancers such as angiosarcomas," says Dr Sam Behjati, first author from the Wellcome Trust Sanger Institute. "Not only will this help the many patients with these cancers and improve treatment strategies, but it will help us understand the full landscape of cancer-causing mutations and the underlying biology."

INFORMATION: Notes to Editors Publication Details Sam Behjati, Patrick S Tarpey, Helen Sheldon et al. (2014) 'Recurrent PTPRB and PLCG1 mutations in angiosarcoma'

Advanced online publication in Nature Genetics, 16 March. Doi: 10.1038/ng.2921

Funding This work was supported by funding from the Wellcome Trust.

Participating Centres 1. Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK
2. Department of Paediatrics, University of Cambridge, Hills Road, Cambridge, CB2 2XY, UK
3. The Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS, UK
4. Human Genome Laboratory, Department of Human Genetics, VIB and KU Leuven, B-3000 Leuven, Belgium
5. Histopathology, Royal National Orthopaedic Hospital NHS Trust, Stanmore, Middlesex, HA7 4LP, UK
6. University College London Cancer Institute, Huntley Street, London, WC1E 6BT, UK
7. Departments of Oncology and Genetics, Oslo University Hospital, N-0310 Oslo, Norway
8. The K.G. Jebsen Center for Breast Cancer Research, University of Oslo, N-0424 Oslo, Norway
9. Institute of Structural and Molecular Biology, Division of Biosciences, University College London, London WC1E6BT, UK
10. Division of Molecular Structure, MRC-National Institute for Medical Research, Mill Hill, London NW7 1AA, UK
11. Department of Pathology, John Radcliffe Hospital, Oxford, OX3 9DS, UK
12. M. D. Anderson Cancer Center, The University of Texas , 1901 East Road, Houston, Texas 77054, USA
13. Bone Tumour Reference Centre, Institute of Pathology, University Hospital Basel, Basel, Institute for Applied Cancer Science, Switzerland
14. Pfizer Oncology, 10555 Science Center Dr, La Jolla, CA, 92121
15. Department of Haematology, Addenbrooke's Hospital, Cambridge, UK
16. Department of Haematology, University of Cambridge, Hills Road, Cambridge, CB2 2XY, UK

Selected Websites

The Wellcome Trust Sanger Institute is one of the world's leading genome centres. Through its ability to conduct research at scale, it is able to engage in bold and long-term exploratory projects that are designed to influence and empower medical science globally. Institute research findings, generated through its own research programmes and through its leading role in international consortia, are being used to develop new diagnostics and treatments for human disease. http://www.sanger.ac.uk

The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. We support the brightest minds in biomedical research and the medical humanities. Our breadth of support includes public engagement, education and the application of research to improve health. We are independent of both political and commercial interests. http://www.wellcome.ac.uk

Contact details Don Powell Media Manager
Wellcome Trust Sanger Institute
Hinxton, Cambridge, CB10 1SA, UK
Tel +44 (0)1223 496 928
Mobile +44 (0)7753 7753 97
Email press.office@sanger.ac.uk

End of Notes to Editors

ELSE PRESS RELEASES FROM THIS DATE:

Mercury contracted more than prior estimates, evidence shows

2014-03-16

New evidence gathered by NASA's MESSENGER spacecraft at Mercury indicates the planet closest to the sun has shrunk up to 7 kilometers in radius over the past 4 billion years, much more than earlier estimates. The new finding, published in the journal Nature Geoscience Sunday, March 16, solves an apparent enigma about Mercury's evolution. Older images of surface features indicated that, despite cooling over its lifetime, the rocky planet had barely shrunk at all. But modeling of the planet's formation and aging could not explain that finding. Now, Paul K. Byrne and ...

Newly identified small-RNA pathway defends genome against the enemy within

2014-03-16

Cold Spring Harbor, NY – Reproductive cells, such as an egg and sperm, join to form stem cells that can mature into any tissue type. But how do reproductive cells arise? We humans are born with all of the reproductive cells that we will ever produce. But in plants things are very different. They first generate mature, adult cells and only later "reprogram" some of them to produce eggs and sperm. For a plant to create reproductive cells, it must first erase a key code, a series of tags attached to DNA across the genome known as epigenetic marks. These marks distinguish ...

Novel gene-finding approach yields a new gene linked to key heart attack risk factor

2014-03-16

ANN ARBOR, Mich. — Scientists have discovered a previously unrecognized gene variation that makes humans have healthier blood lipid levels and reduced risk of heart attacks -- a finding that opens the door to using this knowledge in testing or treatment of high cholesterol and other lipid disorders. But even more significant is how they found the gene, which had been hiding in plain sight in previous hunts for genes that influence cardiovascular risk. This region of DNA where it was found had been implicated as being important in controlling blood lipid levels in ...

Climate change will reduce crop yields sooner than we thought

2014-03-16

A study led by the University of Leeds has shown that global warming of only 2°C will be detrimental to crops in temperate and tropical regions, with reduced yields from the 2030s onwards. Professor Andy Challinor, from the School of Earth and Environment at the University of Leeds and lead author of the study, said: "Our research shows that crop yields will be negatively affected by climate change much earlier than expected." "Furthermore, the impact of climate change on crops will vary both from year-to-year and from place-to-place – with the variability becoming ...

Novel membrane reveals water molecules will bounce off a liquid surface

2014-03-16

Consider the nearest water surface: a half-full glass on your desk, a puddle outside your window, or a lake across town. All of these surfaces represent liquid-vapor interfaces, where liquid meets air. Molecules of water vapor constantly collide with these liquid surfaces: Some make it through the surface and condense, while others simply bounce off. The probability that a vapor molecule will bounce, or reflect, off a liquid surface is a fundamental property of water, much like its boiling point. And yet, in the last century, there has been little agreement on the likelihood ...

Nectar: A sweet reward from plants to attract pollinators

2014-03-16

Stanford, CA— Evolution is based on diversity, and sexual reproduction is key to creating a diverse population that secures competitiveness in nature. Plants had to solve a problem: they needed to find ways to spread their genetic material. Flying pollinators—insects, birds, and bats—were nature's solution. Charles Darwin's "abominable mystery" highlighted the coincidence of flowering plant and insect diversification about 120 million years ago and ascribed it to the coordinated specialization of flowers and insects in the context of insects serving as pollen carriers. ...

Bionic plants

2014-03-16

CAMBRIDGE, MA -- Plants have many valuable functions: They provide food and fuel, release the oxygen that we breathe, and add beauty to our surroundings. Now, a team of MIT researchers wants to make plants even more useful by augmenting them with nanomaterials that could enhance their energy production and give them completely new functions, such as monitoring environmental pollutants. In a new Nature Materials paper, the researchers report boosting plants' ability to capture light energy by 30 percent by embedding carbon nanotubes in the chloroplast, the plant organelle ...

Honey is a new approach to fighting antibiotic resistance: How sweet it is!

2014-03-16

DALLAS, March 16, 2014 — Honey, that delectable condiment for breads and fruits, could be one sweet solution to the serious, ever-growing problem of bacterial resistance to antibiotics, researchers said here today. Medical professionals sometimes use honey successfully as a topical dressing, but it could play a larger role in fighting infections, the researchers predicted. Their study was part of the 247th National Meeting of the American Chemical Society (ACS), the world's largest scientific society. The meeting, attended by thousands of scientists, features more ...

Advance toward developing an oral pain reliever derived from debilitating snail venom

2014-03-16

DALLAS, March 16, 2014 — Scientists reported today they have created at least five new experimental substances — based on a tiny protein found in cone snail venom — that could someday lead to the development of safe and effective oral medications for treatment of chronic nerve pain. They say the substances could potentially be stronger than morphine, with fewer side effects and lower risk of abuse. "This is an important incremental step that could serve as the blueprint for the development of a whole new class of drugs capable of relieving one of the most severe forms ...

Nikki Antwine Starring in "Just As I Am"

2014-03-16

Latrecia (Nikki) Antwine is excited to make her acting debut in the play "Just As I Am", written, directed and produced by Curtis Von of Acting Bad Productions. It explores the lives of a group of professional women with very different personalities who all belong to an organization celebrating the curvy diva. Through the exploration of the actresses' characters, the audience will discover how when women unite through a common denominator they can build confidence, self-awareness, and in turn, pay it forward. Throughout the play, the women will end up discovering ...

Computing leaders propose measures to combat tech-facilitated intimate partner violence, human trafficking, and child exploitation

Sometimes, when competitors collaborate, everybody wins

EU Flagship project DORIAN GRAY to use pioneering AI and avatar technology to uncover links between cardiovascular disease (CVD) and mild cognitive impairment (MCI) to improve healthy ageing and survi

Cancer therapy may be too targeted

ELSE PRESS RELEASES FROM THIS DATE:

LAST 30 PRESS RELEASES: