Scientists Uncover New Potential For Targeted Cancer Treatment

Main Category: Cancer / Oncology
Article Date: 16 Sep 2009 - 5:00 PDT

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Breakthrough Breast Cancer scientists have discovered that a new cancer treatment could be used for more types of cancer than previously thought, potentially helping thousands of cancer patients in the UK each year.

PARP inhibitors, including the new drug, olaparib, which Breakthrough Breast Cancer and Institute of Cancer Research (ICR) scientists helped develop, are already showing considerable promise in clinical trials for cancer linked to BRCA mutations, including some breast and ovarian cancers.

Scientists from the Breakthrough Breast Cancer Research Centre at the ICR have now shown that PARP inhibitors can also kill cancer cells with a faulty PTEN gene. Results published today (16 September) in the journal EMBO Molecular Medicine showed that cells with faulty PTEN genes were up to 25 times more sensitive to PARP inhibitors than cells with normal PTEN.

Faults in the PTEN gene are common in a range of cancers, accounting for between 30 and 80 percent of breast, prostate, melanoma (skin), endometrial (womb) and colon cancers. Nearly 46,000 women are diagnosed with breast cancer in the UK each year, with just under 12,000 women dying of the disease.

Professor Alan Ashworth, Director of the Breakthrough Breast Cancer Research Centre at the ICR, said: "These results are exciting because they show that PARP inhibitors are potentially a powerful targeted treatment with few side effects which may help a broad range of cancer patients.

"Clinical trials have already shown the potential of PARP inhibitors for patients with tumours caused by faulty BRCA genes. We now need to test whether the promising results from this study can be matched in the much larger group of patients with PTEN-related tumours."

The use of PARP inhibitors is part of a novel approach to cancer therapy called synthetic lethality. A cell with a PTEN fault relies on a protein called PARP to keep its DNA undamaged. PARP inhibitors work by blocking PARP, and when combined with defective PTEN, causes the cancer cell to die. This means the tumour should either stop growing or get smaller. Due to the drug working in a targeted way, it kills cancer cells while leaving healthy cells relatively unaffected, which means fewer side effects for patients.

Patients with inherited forms of advanced breast, ovarian and prostate cancers - caused by faulty BRCA1 and BRCA2 genes - have already benefited from PARP inhibitors in a recently published Phase I clinical trial. Despite having previously received many standard therapies, more than half of the patients' tumours shrank or stabilised, with one of the first patients to be given the treatment still in remission after two years. BRCA-related tumours make up about 5 percent of breast cancer cases.

Dr Chris Lord, who led the research with Prof. Ashworth at the Breakthrough Breast Cancer Research Centre at the ICR, said: "This new class of drugs could potentially make a big difference for many thousands of cancer patients, including some with very limited treatment options. It shows Breakthrough's focus on turning lab research into patient benefit as quickly as possible is having an impact."

Professor Peter Rigby, Chief Executive of the ICR, said: "This is an exciting development in the use of PARP inhibitors, showing that they could benefit far more patients than previously believed. The ICR is proud to have been involved in all stages of the development of these drugs and we look forward to further clinical trials and to identifying patients with other types of cancers who could benefit."

Breast Cancer

- Breast cancer is the most commonly diagnosed cancer in the UK - nearly 46,000 women and around 300 men are diagnosed every year.
- Breast cancer accounts for nearly 1 in 3 of all female cancers and one in nine women in the UK will develop breast cancer at some point in their lifetime.
- The good news is that more women than ever in the UK are surviving breast cancer thanks to better awareness, better treatments and better screening.

Breakthrough Breast Cancer

Breakthrough Breast Cancer funds ground-breaking research, campaigns for better services and treatments and raises awareness of breast cancer. Through this work the charity believes passionately that breast cancer can be beaten and the fear of the disease removed for good.
Under the directorship of Professor Alan Ashworth FRS, the Breakthrough Research Centre now has 120 world-class scientists and clinicians tackling breast cancer from all angles - from understanding the normal growth and development of the breast, how breast cancer arises and how the cancer spreads, to treatment and ultimately disease prevention. Scientists at the Breakthrough Research Centre have a range of expertise and approaches and together they are working towards a common goal: a future free from the fear of breast cancer.
Find more information at http://www.breakthrough.org.uk or call free on 08080 100 200.

The Institute of Cancer Research

The Institute of Cancer Research is Europe's leading cancer research centre with expert scientists working on cutting-edge research. In 2009, the ICR marks its 100 years of groundbreaking research into cancer prevention, diagnosis and treatment. The ICR is home to the world's leading academic drug development team, which has developed many drugs now used as standard cancer treatments. It continues to be at the forefront of drug development, discovering an average of two preclinical candidates each year over the past five years. In December 2008, the ICR was ranked as the UK's leading academic research centre by the Times Higher Education's Table of Excellence, based on the results of the Higher Education Funding Council's Research Assessment Exercise. The ICR is a charity that relies on voluntary income, for more information visit http://www.icr.ac.uk.

EMBO Molecular Medicine

EMBO Molecular Medicine is a peer-reviewed journal, dedicated to the publication of original, cutting-edge research in the field of Molecular Medicine. Molecular Medicine is a rapidly-growing area of research at the interface between clinical research and basic biology. The Journal publishes research articles and reviews relevant to all fields of clinical medicine and their related research areas in basic biology. The European Molecular Biology Organization (EMBO) promotes excellence in molecular life sciences in Europe by recognising and fostering talented scientists, empowering them to advance the field of molecular biology. For more information please visit http://www.embomolmed.org.

EMBO

The European Molecular Biology Organization (EMBO) promotes excellence in molecular life sciences by recognizing and fostering talented scientists, empowering them to advance the life sciences to understand how life works and share knowledge to help address the challenges of a changing world. For details about EMBO and its activities please visit http://www.embo.org.

Source
The Institute of Cancer Research