Study finds biological clue in brain tumor development
(18 March 2009: VIDYYA MEDICAL NEWS SERVICE) -- Scientists at The University of Nottingham have uncovered a vital new biological clue that could lead to more effective treatments for a children’s brain tumor that currently kills more than 60 per cent of young sufferers.
Clinician –scientists at the University’s Children’s Brain tumor Research Centre, working on behalf of the Children’s Cancer and Leukaemia Group (CCLG), have studied the role of the WNT biological pathway in central nervous system primitive neuroectodermal tumors (CNS PNET), a type of brain tumor that predominantly occurs in children and presently has a very poor prognosis.
In a paper published in the British Journal of Cancer, they have shown that in over one-third of cases, the pathway is ‘activated’, suggesting that it plays a role in tumor development. The research also highlighted a link between WNT pathway activation and patient survival — patients who had a CNS PNET tumor that was activated survived for longer than those without pathway activation.
The reason for the link between WNT pathway activation and better patient prognosis is as yet unclear. It could be that these tumors represent a less aggressive subset or that pathway activation itself actually harms the tumor. However, the pathway could represent an important new target for the treatment of more effective drugs, with fewer side effects.
Senior author Professor Richard Grundy, from the Children’s Brain tumor Research Centre, said: “The principal aim of our research is to reduce the morbidity and mortality of children with central nervous system tumors through improved understanding of tumor biology. Following on from this, we need to translate this knowledge into effective new treatments for brain tumors through the development and assessment of accurately targeted treatments that will cause fewer side effects than conventional chemotherapy or radiotherapy and be more effective. The ultimate aim is to develop ‘drugs’ that target just the abnormal genes in cancer cells, rather than the current norm which involves the indiscriminate destruction of dividing cells which might be healthy or malignant. Overall, this is an important finding in a poorly understood, poor prognosis disease, which we hope, in time, will lead to the development of new treatments for CNS PNETs.
“We hope our findings will lead to a more detailed understanding of CNS PNETS, which is crucial if we are to ensure each child receives the most appropriate treatment for their disease and that we reduce the number of children in which their cancer recurs.”
In total, around 450 children and young adults under 18 years are diagnosed with a brain tumor each year in the UK. Overall, 60 per cent of children with the cancer in the UK can be successfully treated, but survival for CNS PNETs is less than 40 per cent.
• Funding was provided by the Connie and Albert Taylor Trust, The Samantha Dickson Brain tumor Trust, the Brain tumor Research Fund Birmingham Children’s Hospital Special Trustees.
• The paper, An Investigation of WNT Pathway Activation and Association with Survival in Central Nervous System Primitive Neuroectodermal tumors (CNS PNET) by HA Rogers, S Miller, J Lowe, M-A Brundler, B Coyle and RG Grundy is published in the latest edition of the British Journal of Cancer.
About the Children’s Cancer and Leukaemia Group
Cancer Research UK is the major funding provider of the Children's Cancer and Leukaemia Group and funds the UK clinical trials work of the group in 21 paediatric centres throughout the British Isles. The Children's Cancer and Leukaemia Group is the national professional body responsible for the organisation, treatment and management of virtually all children with cancer in the UK. The group is acknowledged as one of the world's leading childhood cancer clinical trial groups who have made a significant contribution to the international success in treating childhood cancer, resulting in improvements in survival.
British Journal of Cancer
The BJC is owned by Cancer Research UK. Its mission is to encourage communication of the very best cancer research from laboratories and clinics in all countries. Broad coverage, its editorial independence and consistent high standards have made BJC one of the world's premier general cancer journals. www.bjcancer.com.
The University of Nottingham
The University of Nottingham is ranked in the UK's Top 10 and the World's Top 100 universities by the Shanghai Jiao Tong (SJTU) and Times Higher (THE) World University Rankings.
More than 90 per cent of research at The University of Nottingham is of international quality, according to RAE 2008, with almost 60 per cent of all research defined as ‘world-leading’ or ‘internationally excellent’. Research Fortnight analysis of RAE 2008 ranks the University 7th in the UK by research power. In 27 subject areas, the University features in the UK Top Ten, with 14 of those in the Top Five.
The University provides innovative and top quality teaching, undertakes world-changing research, and attracts talented staff and students from 150 nations. Described by The Times as Britain's ‘only truly global university’, it has invested continuously in award-winning campuses in the United Kingdom, China and Malaysia. Twice since 2003 its research and teaching academics have won Nobel Prizes. The University has won the Queen's Award for Enterprise in both 2006 (International Trade) and 2007 (Innovation — School of Pharmacy), and was named ‘Entrepreneurial University of the Year’ at the Times Higher Education Awards 2008.
Nottingham was designated as a Science City in 2005 in recognition of its rich scientific heritage, industrial base and role as a leading research centre. Nottingham has since embarked on a wide range of business, property, knowledge transfer and educational initiatives (www.science-city.co.uk) in order to build on its growing reputation as an international centre of scientific excellence. The University of Nottingham is a partner in Nottingham: the Science City.
Cancer: Another step towards medication
The gene Myc is an important factor for the growth of organisms by cell division. It causes the production of a protein which, as a transcription factor, controls the expression of up to 15 % of all human genes. When this gene mutates to an oncogene, the cell proliferates excessively and apoptosis is inhibited. Thereby the gene plays a decisive role in the development of many tumors. The problem is that pharmacological substances do not target Myc as it does not have enzymatic activity of its own. Thus, scientists worldwide are trying to find alternative ways to inhibit this oncogene. A team of scientists led by Klaus Bister and Markus Hartl of the Institute of Biochemistry and the Centre for Molecular Biosciences of the University of Innsbruck may have made an important step towards achieving this goal.
Suppressing pathological cell growth
For the first time, the scientists have shown that Myc suppresses the expression of the gene BASP1. This evidence prompted them to test the effect of BASP1 on the oncogene. In cell experiments they proved that BASP1 specifically inhibits the uncontrolled proliferation of Myc. „Until now the precise biochemical function of BASP1 is unknown", Professor Bister explains. „However, in our experiments we have found clear evidence that Myc-induced cell transformation can be specifically inhibited by BASP1, and consequently, the gene functions as a tumor suppressor." This finding may facilitate the development of new drugs which keep the development of tumors under control.
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