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

There is clear evidence that lifestyle choices affect the incidence and treatment of cancer, according to a study published in the current issue of American Journal of Lifestyle Medicine (AJLM).

The article “Lifestyle Interventions in the Prevention and Treatment of Cancer” looks at recent research on the five most common forms of cancer (lung, colorectal, breast, prostate and skin) and how some risk factors for these cancers can be lifestyle based and therefore controllable through alterations in human behavior. A Webinar based on the article will be moderated by James M. Rippe, MD, Editor-in-Chief of AJLM, and presented by lead author Clarence H. Brown III, MD, president and CEO of M.D. Anderson Cancer Center Orlando. Participants can earn 1 CME while learning about:

• lifestyle interventions that have been shown to be effective in preventing cancers

• recent evidence for specific lifestyle behaviors for specific cancers
• how to counsel patients for appropriate lifestyle behaviors to lower cancer risk

“While a universal cure for all types of cancer is still not in the foreseeable future,” write the authors in the article, “changes in lifestyle - adhering to a healthy diet, regular exercise, and avoiding smoking and excessive exposure to ultraviolet radiation - can decrease the incidence of cancer.”

The Webinar: “Lifestyle Interventions in the Prevention and Treatment of Cancer,” sponsored by Orlando Health, is being presented by Clarence H. Brown III, MD on Tuesday, October 6, 2009 from 2:00-3:00 P.M. EDT. This educational activity will be worth 1.0 AMA PRA Category 1 Credits™. For more information or to register, please visit http://ajl.sagepub.com.

The AJLM article, “Lifestyle Interventions in the Prevention and Treatment of Cancer,” written by Clarence H. Brown III, MD, Said M. Baidas, MD, Julio J. Hajdenberg, MD, Omar R. Kayaleh, MD, Gregory K. Pennock, MD, Nikita C. Shah, MD, and Jennifer E. Tseng, MD, is being made available by SAGE for a limited time at http://ajl.sagepub.com/cgi/reprint/3/5/337.

Source:
Jim Gilden

SAGE Publications

The USC Epigenome Center has been awarded a $10.4 million National Cancer Institute grant that is expected to pave the way for more effective treatment and diagnosis for cancer patients.

The support for the USC Epigenome Center, which is affiliated with the USC Norris Comprehensive Cancer Center and the Keck School of Medicine of USC, will fund a collaborative effort with Johns Hopkins University to collect epigenomic data from all major types of cancer over the next five years.

The grant is part of a $5 billion infusion of new funds for cancer research and job creation announced today by President Barack Obama at the National Institutes of Health. The funds for the National Institutes of Health will come from the $787 billion economic stimulus package.

The epigenomic data collected will contribute to The Cancer Genome Atlas, a long-term genome characterization and sequencing project funded by the National Cancer Institute and the National Human Genome Research Institute. The project is designed to provide a comprehensive “map” of molecular changes in cancer.

“The data we produce and analyze will lead to new targets for drug development and a better understanding of why some patients respond better to certain drug treatments than others,” said Peter W. Laird, director of the USC Epigenome Center and principal investigator along with Stephen Baylin of Johns Hopkins.

The Cancer Genome Atlas will produce and analyze data on several types of molecular changes, including mutations, chromosomal copy number alterations and gene expression. The USC Epigenome Center will be responsible for all epigenetic data production.

“The Cancer Genome Atlas will look at as many as 500 different samples of tumors and tissues from each cancer type to map the diversity of molecular changes within and between the different types of cancer,” said Peter Jones, director of the USC Norris Comprehensive Cancer Center and co-investigator on the grant. “It’s a huge operation and a wonderful boost to our cancer research program.”

Epigenomics is the study of how parts of the genome are packaged and marked to indicate whether genes are available for use in a particular type of cell or tissue.

Source
University Of Southern California

HOUSTON, May 12 — Confounding the common epidemiological wisdom, urban dwellers had a higher risk of four common, late-stage cancer diagnoses than their rural counterparts in a new, population-based analysis.

• Explain to patients that this study showed that the risk of late-stage cancer diagnosis was highest in the largest city and decreased as residents lived in more rural areas.
• Note that the findings were based on an analysis of cancer epidemiology in one state.

Residents of the most urbanized areas had the highest risk of breast, colorectal, lung, and prostate cancer, Sara McLafferty, Ph.D., and Fahui Wang, Ph.D., of the University of Illinois Urbana-Champaign, reported online in Cancer.

Cancer risk decreased with increasingly rural residency, except for a slight upturn in the most isolated communities.

“We observe a reversal of the commonly held view that risks are highest for rural residents,” the authors concluded.

“The concentration of health disadvantage in highly urbanized places emphasizes the need for more extensive urban-based cancer screening and education programs, especially programs targeted to the most vulnerable urban populations and neighborhoods.”

The authors identified several variables that could account for some of the variability. However, some findings had no ready explanations. For example, residents of large towns in rural areas consistently had lower cancer risks.

Data on urban-rural cancer disparities have been mixed. Authorities in the field generally supported the notion that residents of rural areas had a greater risk of late-stage diagnosis because of reduced access to screening services.

The authors continued the assessment in an analysis that focused on the rural-urban gradient of late-stage cancer risk in Illinois for 1998 through 2002. Using data from the State of Illinois Cancer Registry, they limited the analysis to four major types of cancer: breast, colorectal, lung, and prostate.

For the study period, the authors determined that late-stage diagnosis accounted for 36.9% of breast cancers, 62.9% of breast cancers, 79.7% of lung cancers, and 15.6% of prostate cancers.

To analyze late-stage diagnosis by geographic area, the authors used a modified version of the Rural-Urban Commuting Areas (RUCA) classification system developed by the U.S. Office of Rural Health Policy.

The modifications resulted in five classifications: Chicago, Chicago suburbs, other metropolitan areas, large towns (population 10,000 to 50,000), and rural areas (population <10,000).

Analysis of late-stage cancer diagnosis by the five geographic areas revealed a “clear and remarkably consistent rural-urban gradient in late-stage risk,” the authors said. “Risk is highest in Chicago, decreases in the less urbanized zones, and reaches a nadir in other metropolitan areas and large towns.”

The risk increased somewhat among patients living in the areas classified as rural, resulting in a reverse-J gradient along the urban-rural continuum. The gradient held up for all four types of cancer.

The gradients were steepest for breast, colon, and lung cancer, all of which had the lowest odds ratios in large towns and the highest ratios in Chicago. As compared with Chicago, the odds ratio for large towns ranged between 0.71 and 0.79 for those three cancers.

Age and racial/ethnic variation accounted for some of the disparities. However, some of the disparities persisted in multivariate analysis that accounted for the differences.

As an example, the authors noted that “all other factors being equal, patients who live outside the Chicago area are 25% to 35% less likely than their Chicago-area counterparts to present with late-stage lung cancer.”

The authors reported no competing interests.

Primary source: Cancer

Source reference:
McLafferty S, Wang F “Rural reversal? Rural-urban disparities in late-stage cancer risk in Illinois” Cancer 2009; DOI: 10.1002/cncr.24306.