World Cancer Day 2013: Dispelling Myths & Misconceptions About “The Enemy Within”

1.5 million premature cancer deaths could be prevented each year if targets set to reduce non-communicable diseases are met by 2025.  Today, on World Cancer Day, the Union for International Cancer Control and the International Agency for Research on Cancer reveal the real life impact of achieving this goal.

World Cancer Day 2013

WCD_Logo_RGB_2012 (1)

“… 1.5 million people saved from an early death due to cancer is equal to the entire populations of Philadelphia, Auckland, Barcelona or Maputo each and every year.”

World Cancer Day is the one initiative under which the entire world can unite in the fight against the global cancer epidemic.It takes place every year on February 4th. World Cancer Day aims to save millions of preventable deaths each year by raising awareness and education about cancer, and pressing governments and individuals across the world to take action against the disease.

World Cancer Day is an initiative of the Union for International Cancer Control (UICC), a leading international non-governmental organization dedicated to the prevention and control of cancer worldwide. Founded in 1933 and based in Geneva, UICC’s growing membership of over 765 organizations across 155 countries, features the world’s major cancer societies, ministries of health, research institutes, treatment centers, and patient groups. Additionally, the organization is a founding member of the NCD Alliance, a global civil society network that now represents almost 3,000 organizations in 170 countries.

Target “25 by 25:” Reduce 25% of Premature Non-Communicable Disease Deaths by 2025

The UICC and the International Agency for Research on Cancer (IARC) today announced that 1.5 million lives which would be lost to cancer, could be saved each year if decisive measures are taken to achieve the World Health Organization’s (WHO) “25 by 25” target; to reduce premature deaths due to non-communicable diseases (NCDs), including cancer, by 25% by 2025.

Currently, 7.6 million people die from cancer worldwide every year, out of which, 4 million people die prematurely (aged 30 to 69 years). So unless urgent action is taken to raise awareness about the disease and to develop practical strategies to address cancer, by 2025, this is projected to increase to an alarming 6 million premature cancer deaths per year.

“The estimate of 1.5 million lives lost per year to cancer that could be prevented must serve to galvanize our efforts in implementing the WHO’s ‘25 by 25’ target,” said Dr.  Christopher Wild, Director of IARC. “There is now a need for a global commitment to help drive advancements in policy and encourage implementation of comprehensive National Cancer Control Plans. If we are to succeed in this, we have a collective responsibility to support low- and middle-income countries who are tackling a cancer epidemic with insufficient resources.”

The 1.5 million lives lost per year represent 25% of the estimated 6 million premature cancer deaths that will occur by 2025, and the 6 million figure is itself based on population projections of current numbers and aging.

“Cancer — Did You Know?”

On World Cancer Day, UICC and its members are urging the public and governments alike to speak out with one voice to dispel damaging myths and misconceptions on cancer. Under the theme “Cancer – Did you know?” individuals and communities are encouraged to shed light on four key cancer “myths” and the corresponding “truth” via the UICC World Cancer Day Facebook App.

Myth #1: Cancer is just a health issue.

Truth #1: Cancer is not just a health issue. It has wide-reaching social, economic, development and human rights implications.

———-

Myth #2: Cancer is primarily a disease of the wealthy, elderly, and developed countries.

Truth #2: Cancer is a global epidemic, affecting all ages and socio-economic groups, with developing countries bearing a disproportionate burden.

———-

Myth #3: Cancer is a death sentence.

Truth #3: Many cancers that were once considered a death sentence can now be cured and for many more people their cancer can now be treated effectively.

———-

Myth #4: Cancer is my fate.

Truth #4: With the right strategies, at least 30% of cancer cases can be prevented based on current knowledge.

———-

Mr. Cary Adams, UICC Chief Exective Officer said:

“This World Cancer Day UICC, its members and partners urge everyone from individuals to governments to take a stand against damaging myths on cancer. By truly understanding this deadly disease, governments can develop appropriate strategies to reduce premature deaths and reach the WHO ‘25 by 25’ goal. The figures today announced by IARC and UICC reveal the fundamental human value of achieving this target. 1.5 million people saved from an early death due to cancer is equal to the entire populations of Philadelphia, Auckland, Barcelona or Maputo each and every year.”

What Can You Do?

In 2008, UICC developed the World Cancer Declaration as a tool to help bring the growing cancer crisis to the attention of government leaders and health policymakers. The 11 Declaration targets, designed to significantly reduce the global cancer burden by 2020, have served as the basis for UICC recommendations to the WHO. This year’s goal — #5 Declaration target — is to dispel damaging cancer myths and misconceptions. The Declaration, with more than half a million signatories, has also been instrumental in generating political will for cancer control targets both at the United Nations and grassroots levels. In close collaboration with the NCD Alliance, UICC played a key role recently in securing WHO’s global health target of a 25% reduction in premature deaths from NCDs by 2025 (known as “25 by 25”), at the World Health Assembly in May 2012 – demonstrating the important role advocacy plays in the global flight against cancer.

To sign the World Cancer Declaration, click here.

To download the World Cancer Day Facebook App, and play your part in reducing the unacceptable burden of cancer, visit https://apps.facebook.com/world_cancer_day.

Review and circulate the cancer truth fact sheets hyperlinked above under the “Cancer — Did You Know?” section of this article.

For more ideas on how you can get involved and take local action against the global crisis of cancer, visit worldcancerday.org.

Understanding Cancer:  “The Enemy Within” Documentary

In the documentary posted below, Vivienne Parry OBE tells the incredible story of our fight against cancer over the last 50 years. Through the eyes of scientists, researchers, and patients, we see how far we have come and how far we have yet to go, including contributions from Professor Robert Weinberg, Professor Umberto Veronesi, Lord Ara Darzi, Cancer Research UK, David Nathan, M.D., Brian Druker, M.D., and many more.

The film is a non-commercial, editorially independent piece of work which has been supported by Cancer Research UK and funded by an educational grant from Roche. The purpose is to educate and inform those who are affected by cancer. It’s now freely available to all who may want to use it, so please feel free to embed on your own websites and share as you see fit.

U.K. Researchers Launch Clinical Trial of Mercaptopurine (6-MP) In Women with Hereditary Breast and Ovarian Cancer

A Cancer Research UK-funded clinical trial of a new drug for patients with advanced breast or ovarian cancer due to inherited BRCA gene mutations has been launched at the Experimental Cancer Medicine Centre at the University of Oxford.

A Cancer Research UK-funded trial of a new drug for patients with advanced breast or ovarian cancer due to inherited BRCA gene faults has been launched at the Experimental Cancer Medicine Centre at the University of Oxford (OxFord ECMC).

Mutations in the BRCA 1 (BReast CAncer-1) and BRCA 2 genes are thought to account for around 2-5 percent of all breast cancer cases. Women carrying the BRCA1 and BRCA2 mutation have a 45-65 percent chance of developing breast cancer, and a 20-45 percent chance of developing ovarian cancer, by the age of 70. Genetic testing for faulty BRCA genes is available for women with a very strong family history.

DNA damage, due to environmental factors and normal metabolic processes inside the cell, occurs at a rate of 1,000 to 1,000,000 molecular lesions per cell per day. A special enzyme (shown above in color), encircles the double helix to repair a broken strand of DNA. Without molecules that can mend DNA single strand and double strand breaks, cells can malfunction, die, or become cancerous. (Photo: Courtesy of Tom Ellenberger, Washington University School of Medicine in St. Louis)

Cells lacking a properly functioning BRCA1 or BRCA2 gene  are less able to repair DNA damage. These defective cells are more sensitive to (i) platinum-based chemotherapy drugs such as cisplatin – which work by causing double-stranded DNA breaks, and (ii) PARP inhibitors, a newer class of drugs which prevent cells lacking a properly functioning BRCA gene from being able to repair damaged DNA. PARP inhibitors have shown promise in clinical trials but, as with most drugs, resistance can develop meaning some women can stop responding.

This trial, led by a team based at the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, is looking at a drug called “6MP” (a/k/a mercaptopurine; brand name: Purinethol), which is already used to treat leukemia and is often given in combination with another chemotherapy drug called “methotrexate.”

Earlier studies involving cells grown in the laboratory suggest that a class of drugs called “thiopurines,” which includes 6MP, are effective at killing cancer cells lacking BRCA – a gene which significantly increases the risk of breast and ovarian cancer – even after they have developed resistance to treatments like PARP inhibitors and cisplatin.

This trial is one of a growing number looking at matching patients to the most appropriate treatment based on their genetic makeup and that of their cancer – an approach known as “personalized medicine.”

If successful, the results will pave the way for a larger Phase 3 clinical trial, which could lead to an additional treatment option for the 15 out of every 100 women with breast and ovarian cancers, which are caused by faults in the BRCA1 or BRCA2 gene.

Trial leader Dr. Shibani Nicum, a gynecology specialist based at the Oxford ECMC, and a researcher in Oxford University’s Department of Oncology, said: “PARP inhibitors are a powerful new class of drugs developed specifically to target tumors caused by BRCA 1 and BRCA2 faults, but drug resistance remains a problem. We hope that the very encouraging results we have seen in early laboratory studies involving 6MP will lead to increased treatment options for these patients in the future.”

U.K. trial participant Suzanne Cole, 54, from Newbury, has a strong history of ovarian cancer in her family, with her sister, mother and grandmother all having been diagnosed with suspected cases of the disease at a relatively young age. But, it was not until many years later, after she herself was diagnosed with cancer, that doctors were able to trace the cause of this back to a BRCA1 mutation in her family.

Suzanne Cole said: “I was diagnosed in 2009 and initially had surgery then chemotherapy. I was then told about the trial and I went away and studied the information. The doctors were able to answer all my questions and then I agreed to sign up. I’m happy to be a part of this work as it could help others by moving treatments forward.”

Professor Mark Middleton, director of the Oxford ECMC, said: “It’s exciting to see drugs being developed for specific groups of patients who share the same underlying genetic faults in their cancer. Targeted treatments are at the cutting edge of cancer care and we’re proud to be involved in bringing such drugs a step closer to the clinic.”

Dr. Sally Burtles, Cancer Research UK’s director of the ECMC Network, said: “This study helps demonstrate the value of being able to pool subsets of patients who share specific rare faults in their tumor from a UK-wide network of Experimental Cancer Medicine Centres. This will be crucial as we move towards a new era of personalized medicine with treatments targeted according to the individual biological profile of a patient’s cancer.”

For more information on the trial, please visit www.cancerhelp.org.uk, or call the Cancer Research UK cancer information nurses on 0808-800-4040.

Sources:

  • Researchers trial new drug for women with hereditary breast and ovarian cancer, Press Release, Cancer Research UK, August 17, 2011.
  • Issaeva N, et al. 6-thioguanine selectively kills BRCA2-defective tumors and overcomes PARP inhibitor resistance. Cancer Res. 2010 Aug 1;70(15):6268-76. Epub 2010 Jul 14. PubMed PMID: 20631063; PubMed PMCID: PMC2913123.

Advanced MRI Scan May Predict Chemotherapy Benefit In Late Stage Ovarian Cancer Patients After Just One Cycle

Scientists at The Institute of Cancer Research and The Royal Marsden Hospital have developed an advanced type of magnetic resonance imaging (MRI) scan that can detect whether late-stage ovarian cancers are responding to chemotherapy treatment after just one cycle.

Scientists at The Institute of Cancer Research (ICR) and The Royal Marsden Hospital have developed an advanced type of magnetic resonance imaging (MRI) scan that can detect whether late-stage ovarian cancers are responding to chemotherapy treatment after just one cycle, which should help doctors decide whether to continue or alter treatment.

Most ovarian cancers are detected after the tumor has already spread and although patients initially respond well to radical surgery and platinum and taxane-based chemotherapy, most relapse after an average of 18 months. Subsequent treatments generally become less effective as patients build up resistance, so scientists are looking for ways to identify non-responsive patients early in the course of treatment.

Diffusion MRI Diagnostics: Diffusion tensor imaging color map (Photo: Wikipedia)

Nandita deSouza, M.D., Ph.D., Lead Academic Radiologist, The Institute of Cancer Research & The Royal Marsden NHS Foundation Trust.

In a paper published online this week in the journal Radiology, Professor Nandita deSouza and colleagues at the ICR and The Royal Marsden find that a technique called diffusion -weighted MRI can be used to show a change after just one 21- or 28-day treatment cycle.

“This test could allow us to predict after just one month whether a patient will benefit from the full six month course of chemotherapy,” Senior author Professor de Souza from the ICR and The Royal Marsden says. “This would help make decisions on treatment and mean that patients could avoid the unpleasant side-effects of ineffective treatments.”

From November 2008 to September 2010, forty-two women with ovarian cancer had diffusion-weighted MRI scans before and after their first and third cycles of chemotherapy. Each scan was then used to calculate a figure called an Apparent Diffusion Coefficient (ADC), a measurement of water movement within tissue, which is lower in tumor compared to normal tissue. The team found ADCs rose after just one treatment cycle for many women who were later assessed to have benefited from treatment, and did not change for patients who did not respond.

The MRI technique can also help determine the extent of the cancer, as it is able to detect tiny cancer seedlings that have spread from the ovaries into the peritoneum. Importantly, Professor de Souza says that the scans also have the potential to identify individual tumor deposits that are not responding to treatment for which other treatment options including surgical removal can be considered.

First author Dr. Stavroula Kyriazi from the ICR and The Royal Marsden says: “We will be starting a larger trial in four UK hospitals later this year that will assess this technique alongside the current blood tests and scans. We hope to find that it consistently detects the effects of treatment earlier, and that it provides more information about individual tumor sites than standard tests. This test can be done on existing MRI equipment, so if it is found to be effective it could potentially be used to help doctors make treatment decisions for their patients right across the country.”

The research was carried out at the Cancer Research UK and EPSRC (Engineering and Physical Sciences Research Council) Cancer Imaging Centre, Research Data Management and Statistics Unit and Department of Gynecological Oncology at the ICR and The Royal Marsden. The study was funded by Marie Curie Actions, the ICR, Cancer Research UK and EPSRC.

Dr. Julie Sharp, senior science information manager at Cancer Research UK, said: “We hope that this new approach will allow doctors to monitor tumors much more closely in the future and make quicker decisions if treatments aren’t working. Advanced ovarian cancer is difficult to treat and we’re pleased to be funding the next stage of this research that will develop this test further.”

The Institute of Cancer Research (ICR)

  • The ICR is Europe’s leading cancer research center.
  • The ICR has been ranked the UK’s top academic research centre, based on the results of the Higher Education Funding Council’s Research Assessment Exercise.
  • The ICR works closely with partner The Royal Marsden NHS Foundation Trust to ensure patients immediately benefit from new research. Together the two organizations form the largest comprehensive cancer center in Europe.
  • The ICR has charitable status and relies on voluntary income.
  • As a college of the University of London, the ICR also provides postgraduate higher education of international distinction.
  • Over its 100-year history, the ICR’s achievements include identifying the potential link between smoking and lung cancer which was subsequently confirmed, discovering that DNA damage is the basic cause of cancer and isolating more cancer-related genes than any other organization in the world.
  • The ICR is home to the world’s leading academic cancer drug development team. Several important anti-cancer drugs used worldwide were synthezised at the ICR and it has discovered an average of two preclinical candidates each year over the past five years.

For more information visit www.icr.ac.uk.

About the Royal Marsden Hospital

The Royal Marsden opened its doors in 1851 as the world’s first hospital dedicated to cancer diagnosis, treatment, research and education.

Today, together with its academic partner, The Institute of Cancer Research (ICR), it is the largest and most comprehensive cancer center in Europe treating over 44,000 patients every year. It is a center of excellence with an international reputation for groundbreaking research and pioneering the very latest in cancer treatments and technologies. The Royal Marsden also provides community services in the London boroughs of Sutton and Merton and in June 2010, along with the ICR, the Royal Marsden NHS Foundation Trust launched a new academic partnership with Mount Vernon Cancer Centre in Middlesex.

Since 2004, the hospital’s charity, The Royal Marsden Cancer Charity, has helped raise over £50 million to build theatres, diagnostic centres, and drug development units. Prince William became President of The Royal Marsden in 2007, following a long royal connection with the hospital.

For more information, visit www.royalmarsden.nhs.uk.

About Marie Curie Actions

The EU’s Marie Curie Actions provide grants at all career stages from post-graduate level to encourage international mobility among Europe’s best researchers. Every year, through the Marie Curie Actions, the EU gives 8,000 researchers the opportunity to work abroad and stimulates partnerships between research and business. The EU will allocate more than €4.5 billion under the scheme between 2007 and 2013. A total of 50,000 researchers have been supported by the Marie Curie Actions since 1996.

For more information, visit http://ec.europa.eu/research/mariecurieactions/.

About Cancer Research UK

  • Cancer Research UK is the world’s leading cancer charity dedicated to saving lives through research.
  • The charity’s groundbreaking work into the prevention, diagnosis and treatment of cancer has helped save millions of lives. This work is funded entirely by the public.
  • Cancer Research UK has been at the heart of the progress that has already seen survival rates double in the last forty years.
  • Cancer Research UK supports research into all aspects of cancer through the work of over 4,000 scientists, doctors and nurses.
  • Together with its partners and supporters, Cancer Research UK’s vision is to beat cancer.

For further information about Cancer Research UK’s work or to find out how to support the charity, please call 020 7121 6699 or visit www.cancerresearchuk.org.

Sources:

  • Kyriazi S, et. al. Metastatic Ovarian and Primary Peritoneal Cancer: Assessing Chemotherapy Response with Diffusion-weighted MR Imaging–Value of Histogram Analysis of Apparent Diffusion Coefficients. Radiology. 2011 Aug 9. [Epub ahead of print] PubMed PMID: 21828186.
  • Scan Predicts Chemotherapy Benefit After Just One Cycle, Press Release, The Institute of Cancer Research, August 12, 2011.

Inherited Mutations in RAD51D Gene Confer Susceptibility to Ovarian Cancer

Cancer Research UK-funded scientists have discovered that women who carry a faulty copy of a gene called RAD51D have almost a 1-in-11 chance of developing ovarian cancer. The finding that inherited mutations in the RAD51D gene confer susceptibility to ovarian cancer was reported in a study published online in Nature Genetics on August 7, 2011.

Cancer Research UK-funded scientists have discovered that women who carry a faulty copy of the RAD51D gene have nearly a 1-in-11 chance of developing ovarian cancer. The finding that inherited mutations in the RAD51D gene confer susceptibility to ovarian cancer was reported in a study published online in Nature Genetics on August 7, 2011.

(Photo: Cancer Research UK)

Although hereditary faults in RAD51D are thought to account for less than one in every hundred ovarian cancer cases – fewer than 60 women every year in the UK – this discovery could prove very important in the future in connection with the prevention and treatment of the disease in women who carry the faulty gene.

The team at The Institute of Cancer Research (ICR) examined DNA from women from 911 families with ovarian and breast cancer and compared differences in DNA with a control group of 1,060 people from the general population.

The team discovered eight germline (inherited) gene faults in the RAD51D gene in women with cancer, compared with one in the control group.

Ovarian cancer is the fifth most common cancer in women with approximately 6,500 cases diagnosed annually in the UK. The researchers estimate that RAD51D gene faults are present in almost one percent of women with ovarian cancer; that is, around 50 UK women each year.

Around one woman in 70 in the general population is at risk of developing ovarian cancer, but for those with a RAD51D gene fault this risk is increased to 1-in-11 – making these women six times more likely to develop the disease. The RAD51D gene fault also caused a slight increase in the risk of breast cancer.

The RAD51D gene is important for repairing damaged DNA. When the RAD51D gene is faulty, a key DNA repair pathway known as “homologous recombination” (HR) fails. This means DNA damage is not fixed and DNA faults build up in cells which make them more likely to turn into cancer.

The UK team also showed that cells with faulty RAD51D can be selectively destroyed by a relatively new class of cancer drugs called “PARP (poly (ADP-ribose) polymerase) inhibitors.” When the researchers tested the drugs on cells with the faulty RAD51D gene, they observed a dramatic effect – nearly 90 percent of the cells died, compared with just 10 percent of cells with fully functional RAD51D. These drugs are showing great promise in clinical trials for the treatment of breast and ovarian cancers with faults in the BRCA1 and BRCA2 genes, which are also important for repairing damaged DNA.

Professor Nazneen Rahman

Cancer Research UK-funded scientist and study author Professor Nazneen Rahman, head of the Division of Genetics and Epidemiology at The Institute of Cancer Research and The Royal Marsden cancer center, said:

“Women with a fault in the RAD51D gene have a 1-in-11 chance of developing ovarian cancer. At this level of risk, women may wish to consider having their ovaries removed after having children, to prevent ovarian cancer from occurring. There is also real hope on the horizon that drugs specifically targeted to the gene will be available.”

Professor Nic Jones

Professor Nic Jones, Cancer Research UK’s chief scientist, said:

“It’s incredibly exciting to discover this high risk gene for ovarian cancer. It’s further evidence that a range of different high risk genes are causing the development of breast and ovarian cancer and we hope there are more waiting to be discovered in different cancers. We believe the results of this research will help inform personalized treatment approaches and give doctors better information about risks of cancer to tell patients.”

Harpal S. Kumar, CEO, Cancer Research UK

Harpal Kumar, Cancer Research UK’s chief executive, said:

“Survival from ovarian cancer has almost doubled in the last 30 years. This landmark discovery is another piece of the jigsaw deepening our understanding of the disease. We hope this will have a significant impact in providing more personalised treatments for patients based on their genetic make-up, saving more lives from ovarian cancer. All of our research is generously funded by the public. This support has allowed us to invest heavily in the identification of DNA changes which paint a picture of which parts of a person’s gene set are linked to cancer. This life-changing discovery exemplifies the importance of this research and the importance of ongoing public support.”

Again, it is important to stress that faults in the RAD51D gene are rare, probably causing fewer than one in every 100 ovarian cancers. Yet for the small proportion of women who carry a faulty RAD51D gene, there is a chance of developing ovarian cancer, thereby making it a significant new finding.

Cancer Research UK is the largest single funder of ovarian cancer research in the UK – last year it spent more than £12 million of public donations on tackling the disease.

The RAD51D gene mutation study findings in relation to ovarian cancer susceptibility add to past evidence which links the gene to the disease. On April 21, 2010, Libby’s H*O*P*E*™ reported that a team of German researchers determined that RAD51C also increases a woman’s risk of breast and ovarian cancer.  Specifically, the identified risk for breast cancer in women with the RAD51C mutation was reported to be 60 percent to 80 percent, while the identified risk for ovarian cancer was 20 percent to 40 percent.

On November 11, 2010, we also reported that a separate group of U.K. researchers concluded that (i) HR-deficient status can be determined in primary ovarian cancer through a “RAD51 assay,” and (ii) such status correlates with in vitro response to PARP inhibition. Accordingly, the researchers concluded that potentially 50 percent to 60 percent of ovarian cancers patients could benefit from PARP inhibitors, but they noted that use of the RAD51 assay as a biomarker requires additional clinical trial testing. Although the RAD51 assay test that was used by these U.K. researchers to examine tumor samples in the laboratory is not yet suitable for routine clinical practice, the U.K. research team hopes to refine it for use in patients.

Sources:

About Cancer Research UK

  • Cancer Research UK is the world’s leading cancer charity dedicated to saving lives through research.
  • The charity’s groundbreaking work into the prevention, diagnosis and treatment of cancer has helped save millions of lives. This work is funded entirely by the public.
  • Cancer Research UK has been at the heart of the progress that has already seen survival rates double in the last forty years.
  • Cancer Research UK supports research into all aspects of cancer through the work of over 4,000 scientists, doctors and nurses.
  • Together with its partners and supporters, Cancer Research UK’s vision is to beat cancer.

For further information about Cancer Research UK’s work or to find out how to support the charity, please call 020-7121-6699 or visit www.cancerresearchuk.org

About The Institute of Cancer Research (ICR)

  • The ICR is Europe’s leading cancer research center.
  • The ICR has been ranked the UK’s top academic research center, based on the results of the Higher Education Funding Council’s Research Assessment Exercise.
  • The ICR works closely with partner The Royal Marsden NHS Foundation Trust to ensure patients immediately benefit from new research. Together the two organisations form the largest comprehensive cancer centre in Europe.
  • The ICR has charitable status and relies on voluntary income.
  • As a college of the University of London, the ICR also provides postgraduate higher education of international distinction.

Over its 100-year history, the ICR’s achievements include identifying the potential link between smoking and lung cancer which was subsequently confirmed, discovering that DNA damage is the basic cause of cancer and isolating more cancer-related genes than any other organization in the world.

For more information visit www.icr.ac.uk

About The Royal Marsden

  • The Royal Marsden is a world-leading cancer centre specializing in cancer diagnosis, treatment, research and education.
  • The Royal Marsden is also partners with The Institute of Cancer Research. Through this partnership, it undertakes groundbreaking research into new cancer drug therapies and treatments. The partnership makes The Royal Marsden the biggest and most comprehensive cancer center in Europe, with a combined staff of 3,500.

UCL Scientists Discover How To Switch On Critical Ovarian Cancer “Protector” Gene & Arrest Tumor Growth

A new University College London study reveals that a gene [EPB41L3] which normally protects against ovarian cancer is switched off in 66% of ovarian cancer cases and switching it back on arrests tumor growth.

A new University College London study reveals that a gene which normally protects against ovarian cancer is switched off in 66% of ovarian cancer cases and switching it back on arrests tumor growth.

The researchers found that the “protector gene,” known as EPB41L3, is inactivated in 65 per cent of ovarian cancers and reactivating the gene halted tumor growth and triggered large numbers of ovarian cancer cells to commit suicide.

The research, co-funded by Cancer Research UK and the gynecological cancer research charity The Eve Appeal, raises the prospect for developing therapies that mimic or restore the function of the gene to kill ovarian cancer cells in a targeted way.

UCL’s Dr. Simon Gayther, who led the study, said:

“Previous studies have found similar ‘protector genes’ but ours is the first to uncover EPB41L3 as a gene specific to ovarian cancer. We also discovered that the gene is completely lost in about two-thirds of the ovarian tumours we looked at. When we switched it back on in these tumours, it had a positive effect in killing cancer cells. This is a very exciting result because it means therapies that mimic or reactivate this gene could be a way to kill many ovarian cancers.”

The scientists, based at UCL’s Institute of Women’s Health, used a cutting-edge approach which involves transferring whole chromosomes into ovarian cancer cells. They found that introducing an additional copy of chromosome 18 boosted the activity of 14 key genes, triggering large numbers of the cancer cells to die.

The scientists examined more than 800 ovarian tumors and found that one of the 14 genes – EPB41L3 – was inactivated in around 66% of malignant ovarian tumors, compared to 24% of benign tumors and 0% of normal ovarian cells.

Reactivating the gene had the same deadly effect on the cancer cells, suggesting that it was the trigger that was causing the cells to self-destruct.

Jane Lyons, CEO of The Eve Appeal, said:

“This research is an exciting step forward – a gene has been identified that can help halt the growth and spread of ovarian cancers. The challenge now is for the researchers and clinicians to find a way to use this new information to increase survival from the disease.”

Dr. Lesley Walker, director of cancer information at Cancer Research UK, said:

“We know that there is a class of genes that protect us from developing cancer. This is an exciting new one specific to ovarian cancer. Advanced ovarian cancer is very difficult to cure, which makes this type of research even more important.”

Sources:

“Shielded” Ovarian Cancer Cells May Survive Chemotherapy

Cancer Research UK scientists have discovered certain ovarian tumor cells that are resistant to chemotherapy can survive a first round of treatment and go on to “re-grow” the cancer.

Cancer Research UK scientists have discovered certain ovarian tumor cells that are resistant to chemotherapy can survive a first round of treatment and go on to “re-grow” the cancer. This could help explain why the disease can be difficult to treat, according to new research published in Oncogene on June 28.

The study, funded by Cancer Research UK, aimed to find out whether it is the chemotherapy itself that causes anti-cancer drug resistance to build in the body – similar to resistance to antibiotics – or if cells that are shielded against cancer treatment grow as part of the initial tumor and are already lying dormant before chemotherapy begins.

Often ovarian cancer can be hard to treat with treatment failing after women initially responded well. The number of women surviving beyond five years is less than 35 per cent.

The researchers compared the characteristics of cell lines from the tumor at the time of diagnosis to cell lines from the same patients once the disease had been treated and become resistant.

Dr. James Brenton, Researcher, Functional Genomics of Ovarian Cancer, Cambridge Research Institute

Dr. James Brenton, study author from the Cancer Research UK’s Cambridge Research Institute, said:

“Ovarian cancer is notoriously hard to treat. Women usually respond well to their first round of chemotherapy with the disease apparently completely removed.  But unfortunately many go on to relapse within six to 24 months. Until now we haven’t known whether they are becoming resistant to the treatment or whether the cells that don’t respond to treatment re-grow the tumour.

By examining the characteristics of ovarian tumours we now think that cells resistant to chemotherapy grow as part of the tumor. This means that when patients have treatment, cells that respond to chemotherapy are destroyed but this leaves behind resistant cells which then form another tumor of completely resistant cells. This seems to explain why successful treatment for relapsed patients is difficult. What needs to be developed now is a therapy designed to target the resistant cells.”

Dr. Lesley Walker, director of science information at Cancer Research UK, said:

“Discoveries like this help to tell us why chemotherapy stops working for some ovarian cancer patients. We hope it will lead to new ways to tackle the disease and increase the number of women that survive this cancer that can be so hard to cure. The next step will be to develop treatment tailored to fight the resistant cells.”

Sources:

PARP Inhibitor Olaparib Benefits Women With Inherited Ovarian Cancer Based Upon Platinum Drug Sensitivity

Olaparib (AZD2281), a new type of cancer drug known as a “PARP inhibitor,” produced promising results in patients with platinum-refractory, platinum-resistant, and platinum-sensitive ovarian cancer linked to an inherited BRCA1 or BRCA2 gene mutation.

A new type of cancer drug — known as a “PARP inhibitor” — produced promising results in patients with ovarian cancer linked to an inherited BRCA1 or BRCA2 gene mutation. The trial results were published online in the Journal of Clinical Oncology on April 19th.

Scientists at The Institute of Cancer Research (ICR) and The Royal Marsden Hospital, working with pharmaceutical company KuDOS Pharmaceuticals, now a subsidiary of AstraZeneca, found the experimental drug olaparib shrank or stabilized tumors in approximately half of ovarian cancer patients possessing BRCA1 or BRCA2 mutations.

The five-year survival rate for ovarian cancer is just 40 per cent as the majority of patients are diagnosed with an advanced form of the disease. Most patients initially respond well to radical surgery and platinum and taxane-based chemotherapy, but relapse after an average of 18 months. Subsequent treatments generally become less effective as patients build up resistance.

Professor Stan Kaye, Head of Section of Medicine, Institute of Cancer Research; Head of Drug Development Unit, The Royal Marsden Hospital; and Cancer Research UK-funded scientist

“There is an urgent need to find new drugs for women diagnosed with ovarian cancer,” says Professor Stan Kaye, Head of the Section of Medicine at the ICR and Head of the Drug Development Unit at The Royal Marsden Hospital and a Cancer Research UK-funded scientist. “Olaparib is still in early-stage testing but the results so far are very encouraging. These findings raise the possibility that carefully selected patients in future may well be offered olaparib as an alternative to chemotherapy during the course of their treatment.”

Between 2005 and 2008, about 50 women with confirmed or suspected BRCA1 or BRCA2 mutations began treatment with olaparib in a dose escalation and single-stage expansion of a Phase I trial. Twenty patients responded with their tumors shrinking or with significant falls in their ovarian cancer marker CA125, or both. The disease also stabilized in three patients. The drug was effective for an average of seven months. Notably, several patients are still taking olaparib (for nearly two years). Drug side-effects were generally mild, especially when compared to current chemotherapy treatments.

Olaparib is a new type of drug known as a PARP inhibitor that works by turning a tumor’s specific genetic defect against itself. In susceptible cells, olaparib prevents the repair of naturally occurring breaks in DNA, which healthy cells are able to repair. Susceptible cancer cells – those with an existing defect in a DNA repair pathway caused by a mutation in the BRCA1 or BRCA2 genes – are unable to repair themselves, and therefore, die.

Platinum-based chemotherapy, particularly carboplatin, is one of the main treatments used for ovarian cancer. When this treatment ceases to be effective, theoretically, olaparib might be less effective too, so the ICR scientists examined whether olaparib would still benefit patients whose response to previous platinum-based drugs was limited. Finding new drugs to treat these “platinum-resistant” ovarian cancer patients (those who relapsed within six months of previous platinum therapy) is a particularly high priority as they have a lower chance of benefiting from re-treatment with chemotherapy and a poorer prognosis.

The research team found that the clinical benefit rate with olaparib was indeed higher — 70% — among patients with “platinum-sensitive disease” (disease recurrence more than six months after previous platinum therapy). Crucially, however, the clinical benefit rate was still 46% in platinum resistant patients.

ICR Study Findings:

  • 50 patients participated in the study (13 had platinum-sensitive disease, 24 had platinum-resistant disease, and 13 had platinum-refractory disease (according to platinum-free interval).
  • 20 patients (40%) achieved complete or partial responses under RECIST (Response Evaluation Criteria in Solid Tumors) criteria and/or tumor marker (CA125) responses.
  • Overall clinical benefit rate (complete response + partial response + stable disease) = 46%.
  • Median response duration was 28 weeks.
  • There was a significant association between the clinical benefit rate and platinum-free interval across the platinum-sensitive, resistant, and refractory patient subgroups (69%, 45%, and 23%, respectively).
  • Analyses indicated associations between platinum sensitivity and extent of olaparib response.
  • CONCLUSION: Olaparib has antitumor activity in BRCA1/2 mutation ovarian cancer, which is associated with platinum sensitivity.

Up to 15 per cent of breast and ovarian cancers have known BRCA1 or BRCA2 mutations on blood testing and, importantly, laboratory data strongly suggests that olaparib may also be effective in cancers linked to DNA repair defects not caused by BRCA1 and BRCA2 mutations. This could apply in about half the cases of the most common histological type of ovarian cancer.

“We have good reason for thinking that the benefit seen with olaparib in BRCA mutation-linked ovarian cancer may well extend to a broader population of patients with this disease,” says Professor Kaye.

Randomised trials of olaparib – in which some patients receive the drug and others a placebo – are underway and results will be available later this year.

KuDOS Pharmaceuticals (a wholly owned subsidiary of AstraZeneca) was the major funder of the trial, along with Cancer Research UK and the National Institute for Health Research. Olaparib was identified and developed at KuDOS Pharmaceuticals and subsequently at AstraZeneca.

PARP Inhibitor Clinical Trials:

To view a list of open ovarian cancer clinical trials that are testing olaparib (AZD2281), click here.

To view a list of open solid tumor clinical trials that are testing olaparib (AZD2281), click here.

To view a list of open ovarian cancer clinical trials that are testing various PARP inhibitors, click here.

To view a list of open solid tumor clinical trials that are testing various PARP inhibitors, click here.

About The Institute of Cancer Research (ICR)

* The ICR is Europe’s leading cancer research centre.

* The ICR has been ranked the UK’s top academic research centre, based on the results of the Higher Education Funding Council’s Research Assessment Exercise.

* The ICR works closely with partner The Royal Marsden NHS Foundation Trust to ensure patients immediately benefit from new research. Together the two organisations form the largest comprehensive cancer centre in Europe.

* The ICR has charitable status and relies on voluntary income, spending 95 pence in every pound of total income directly on research.

* As a college of the University of London, the ICR also provides postgraduate higher education of international distinction.

* Over its 100-year history, the ICR’s achievements include identifying the potential link between smoking and lung cancer which was subsequently confirmed, discovering that DNA damage is the basic cause of cancer and isolating more cancer-related genes than any other organization in the world.

* The ICR is home to the world’s leading academic drug development team. Several important anti-cancer drugs used worldwide were synthesised at the ICR and it has discovered an average of two preclinical candidates each year over the past five years.

For more information visit www.icr.ac.uk.

About The Royal Marsden Hospital

The Royal Marsden opened its doors in 1851 as the world’s first hospital dedicated to cancer treatment, research and education. Today, together with its academic partner, The Institute of Cancer Research, it is the largest and most comprehensive cancer centre in Europe treating over 40,000 patients every year. It is a centre of excellence, and the only NHS Trust to achieve the highest possible ranking in the Healthcare Commission’s Annual Health Check for the third year in a row. Since 2004, the hospital’s charity, The Royal Marsden Cancer Campaign, has helped raise over £43 million to build theatres, diagnostic centres, and drug development units. Prince William became President of The Royal Marsden in 2007, following a long royal connection with the hospital.

For more information, visit www.royalmarsden.nhs.uk

About Cancer Research UK

* Cancer Research UK is the world’s leading charity dedicated to beating cancer through research.

* The charity’s groundbreaking work into the prevention, diagnosis and treatment of cancer has helped save millions of lives. This work is funded entirely by the public.

* Cancer Research UK has been at the heart of the progress that has already seen survival rates double in the last thirty years.

* Cancer Research UK supports research into all aspects of cancer through the work of more than 4,800 scientists, doctors and nurses.

* Together with its partners and supporters, Cancer Research UK’s vision is to beat cancer.

For further information about Cancer Research UK’s work or to find out how to support the charity, please call 020 7121 6699 or visit www.cancerresearchuk.org

About Experimental Cancer Medicine Centre (ECMC)

Experimental Cancer Medicine Centre (ECMC) status has been awarded to 19 centres in the UK that are specialist centres conducting research into new cancer treatments. The aim is to bring together cancer doctors, research nurses and lab scientists to make clinical trials of new treatments quicker and easier. The ECMC initiative is funded by Cancer Research UK and the Departments of Health of England, Scotland, Wales and Northern Ireland. Together they are giving a total of £35 million pounds over five years to the 19 centres. The centres will use this money to run trials of new and experimental treatments. They will also analyse thousands of blood and tissue samples (biopsies) to help find out more about how treatments work and what happens to cancer cells.

Sources: