Ovarian cancer research may pave the way for new treatment approach to benefit tens of thousands
Tumour suppressor initially found in ovarian cancer is inactivated in 8 different cancers
14/02/2012: Ovarian Cancer Action scientists have discovered the mechanism of a potentially important cancer protein that may have major implications for the treatment of not just ovarian cancer but lots of other forms of the disease. This new research describes how “OPCML”, a protein active in normal cells, works to suppress cancer growth, how it is switched off in cancer and demonstrates that a therapy based on replacing the protein at the cell surface may offer a new treatment approach for ovarian and other cancers in the future.
This latest work from a team at the Ovarian Cancer Action’s Research Centre, Imperial College - led by Professor Hani Gabra, Director of the Ovarian Cancer Action Research Centre, Imperial College London - is reported in Cancer Discovery, the prestigious new journal of the American Association for Cancer Research. The study focuses on how “opioid binding protein cell adhesion molecule” (OPCML), a tumour suppressor protein found in normal cells and switched-off in about 80% of all ovarian cancers, works.
Professor Gabra explains, “It is important that in over 1500 patients with 8 different kinds of cancer, almost half showed silencing of OPCML, including colorectal, endometrial, brain, renal and lung cancers. Having the protein retained in sufficient quantities in patients’ cancers appeared to indicate a better outlook for those patients. Our findings demonstrate how OPCML works in normal and cancerous cells, and points towards new approaches to treatment of ovarian cancer.”
The techniques reported in the paper include database analysis and studies of cell lines and tumour-bearing mouse models of ovarian cancer. A main finding centres around demonstrating that OPCML works by switching off a group of proteins that drive cancer called receptor tyrosine kinases (RTKs), proteins with important implications for cancer treatment.
Because OPCML acts on the outside of the cell to suppress tumour growth, restoring its activity by replacing the protein at the cell surface might be a better approach to treatment than other tumor suppressor replacement approaches such as gene therapy that requires delivery right into the cell. Indeed, the paper reports that, in two mouse models of ovarian cancer, giving a form of OPCML protein twice a week inhibited both tumour growth and fluid build up in and around the ovaries (ascites) – a common and unpleasant complication of ovarian cancer.
Conversely, “silencing” the OPCML gene in normal ovarian cells increased the levels of these same RTK proteins, confirming this link between OPCML and RTKs, and caused acceleration of the growth of the previously normal cells.
Future studies will conduct drug development to take these approaches into the clinic. It may ultimately be possible to target several ovarian cancer specific RTKs simultaneously to suppress tumour growth.
With ovarian cancer affecting 6,500 women in Britain every year, and OPCML shown to be involved in others types of cancer, the implications of a protein found absent in a high percentage of human cancers are far reaching.
This study, a collaboration between Ovarian Cancer Action researchers, others at Imperial College and a team at the University of Pennsylvania School of Medicine in Philadelphia, USA, used information from The Cancer Genome Atlas (TCGA) project to confirm the general relevance of OPCML to human cancer.This American venture pools the results of many group’s efforts and makes the data publicly accessible, enabling researchers anywhere in the world to make and validate important discoveries. This way of working fits well with the 9-point action plan for ovarian cancer research recently proposed by Ovarian Cancer Action and published in the journal Nature Reviews Cancer on 23 September 2011, that international consortia such as these are well suited to making data available for sharing via international collaborations.
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Notes to Editors:
Ovarian cancer statistics and facts
- In the UK a woman dies every two hours of ovarian cancer
- 7000 UK women are diagnosed with the disease every year
- It’s the most deadly of the gynaecological cancers
- It is currently the fifth most common cancer among women
- Ovarian cancer has one of the poorest survival rates of all cancers in the UK
There is currently no screening tool, but if found in the early stages up to 90% of women will survive for more than five years. Most women in the UK are not diagnosed until it has already spread, resulting in poor survival rates.
Mature pre and post-menopausal 40 plus women are more likely to be prone to the disease due to life-stage. The majority is unaware of ovarian cancer, and those that are aware know very little about it. They may have suffered the symptoms but confused them for minor ailments.
Ovarian Cancer Action
Ovarian Cancer Action is the UK’s leading ovarian cancer charity, dedicated to improving survival rates for women with ovarian cancer. It funds innovative research into the disease at the Ovarian Cancer Action Research Centre; raises awareness of the symptoms with national awareness campaigns aimed at women and healthcare workers; and gives a voice to those affected by it, acting as an advocate with policymakers, healthcare professionals and scientists.
Ovarian Cancer Action funds a broad range of research to achieve accurate and early detection of ovarian cancer, more effective treatments as well as preventative measures to combat the disease.
Ovarian cancer research 9-Point Action Plan
Leading international scientists are behind a new nine-point action plan for ovarian cancer research entitled Rethinking Ovarian Cancer published in Nature Reviews Cancer. The authors, together with Ovarian Cancer Action, urge colleagues, research funders, charities, industry and patients to back the strategy in beating what remains one of the most deadly cancers for women in the UK and across the world.
The plan is the outcome of a global summit of scientists held earlier this year in the United States and organised by Ovarian Cancer Action, the UK's leading ovarian cancer charity. Professor Fran Balkwill, Chair of the 12th International Helene Harris Memorial Trust (HHMT) Forum in January, described it as one of the most significant meetings in the field for over a decade.
The summit was organised by Ovarian Cancer Action and many of the paper's authors come from the Ovarian Cancer Action Research Centre, Imperial College London.
Please find the paper published in Nature Reviews Cancer here
Ovarian Cancer Action Research Centre
The Ovarian Cancer Action Research Centre is dedicated to defeating ovarian cancer. Its research is focused on developing a better understanding of the disease in order to prevent, diagnose earlier and more accurately, treat more completely and improve length and quality of life of those with the disease.
The Ovarian Cancer Action’s Research Centre at London, Hammersmith Hospital, brings together Imperial College Healthcare clinicians and Imperial College London academics. The Centre is led by Professor Hani Gabra, Professor of Molecular Oncology at Imperial College London, and honorary consultant in medical oncology at Imperial College Healthcare.
Imperial College Healthcare NHS Trust
Imperial College Healthcare comprises Charing Cross, Hammersmith Hospital, Queen Charlotte’s & Chelsea, St Mary’s and Western Eye hospitals. It is one of the largest Trusts in the country, and in partnership with Imperial College London, is the UK’s first Academic Health Science Centre (AHSC). The AHSC was created to take the research discoveries it makes and translate them into new and improved treatments and techniques to directly benefit patients throughout the Trust.
Imperial College London
Consistently rated amongst the world's best universities, Imperial College London is a science-based institution with a reputation for excellence in teaching and research that attracts 14,000 students and 6,000 staff of the highest international quality. Innovative research at the College explores the interface between science, medicine, engineering and business, delivering practical solutions that improve quality of life and the environment - underpinned by a dynamic enterprise culture.
For more information contact: Tania Pearson on 0300 456 4706 and tpearson@ovarian.org.uk