Ovarian cancer is the most deadly of the gynaecological cancers, with approximately 220,000 women diagnosed and 140,000 women dying from the disease each year globally. The approval of Avastin marks a major advance in the treatment of women with ovarian cancer for whom treatment has been limited to surgery and chemotherapy.

“Today’s approval of Avastin marks the first major treatment advance in newly diagnosed ovarian cancer in 15 years,” said Hal Barron M.D., Chief Medical Officer and Head, Global Product Development. “This is the fifth tumor type for which Avastin has been approved in Europe, making it one of few biologic drugs indicated for multiple cancers.”

Avastin has demonstrated in two phase III studies (GOG0218 and ICON7) that women with newly diagnosed advanced ovarian cancer who received Avastin plus chemotherapy and then continued on Avastin alone lived significantly longer without their disease getting worse (progression-free survival) compared to those who received chemotherapy only.

Ovarian cancer is associated with high concentrations of vascular endothelial growth factor (VEGF), a protein associated with tumour growth and spread. Avastin precisely inhibits VEGF, high levels of which are associated with ascites development (excess fluid in the body cavity), disease worsening, and a poorer prognosis in ovarian cancer patients.
About Ovarian Cancer

Ovarian cancer is the eighth most commonly diagnosed cancer in women and the seventh leading cause of cancer death among women worldwide. Annually, over 220,000 women will be diagnosed with ovarian cancer around the world and approximately 140,000 will die from the disease.1

Surgery to remove as much of the tumor as possible, followed by chemotherapy, is a mainstay of treatment but unfortunately, the majority of patients are diagnosed with late stage disease (when the cancer has grown or spread) and they require further treatment.
Avastin in Ovarian Cancer: Research Programme

Roche has an extensive research and clinical trial programme investigating Avastin in patients with ovarian cancer in both the front-line and recurrent setting (when the cancer has returned after initial therapy), in order to help improve treatment outcomes for women with ovarian cancer.

Avastin has so far demonstrated a significant improvement in the time women with ovarian cancer live without the disease getting worse (progression free survival; PFS) in three large phase III studies (GOG 0218 and ICON7 in the front-line setting and OCEANS in the recurrent, platinum-sensitive setting).

This approval will enable the use of Avastin in combination with carboplatin and paclitaxel for the front-line treatment of advanced (FIGO stages IIIB, IIIC and IV) epithelial ovarian, primary peritoneal or fallopian tube cancer for women in Europe. Avastin is administered in addition to chemotherapy for up to 6 cycles of treatment followed by continued use of Avastin as single agent until disease progression or for a maximum of 15 months or until unacceptable toxicity, whichever occurs earlier. The recommended dose of Avastin is 15mg/kg of bodyweight given once every 3 weeks as an intravenous infusion.

Roche is committed to establishing the full potential of Avastin in ovarian cancer through continued research with other agents and in other settings.
About Avastin: Over 5 Years of Transforming Cancer Care

With the initial approval in the USA for advanced colorectal cancer in 2004, Avastin became the first anti-angiogenic therapy made widely available for the treatment of patients with an advanced cancer.

Today, Avastin is continuing to transform cancer care through its proven survival benefit (overall survival and/or progression free survival) across several types of cancer. Avastin is approved in Europe for the treatment of advanced stages of breast cancer, colorectal cancer, non-small cell lung cancer and kidney cancer, and is also available in the US for the treatment of colorectal cancer, non-small cell lung cancer and kidney cancer. In addition, Avastin is approved in the US and over 30 other countries for the treatment of patients with glioblastoma (a type of brain cancer). Avastin is also approved in Japan for the treatment of inoperable or recurrent breast cancer. Avastin is the only anti-angiogenic therapy available for the treatment of these numerous advanced cancer types, which collectively cause over 2.5 million deaths each year.

Avastin has made anti-angiogenic therapy a fundamental pillar of cancer treatment today – over one million patients have been treated with Avastin so far. A comprehensive clinical programme with more than 500 ongoing clinical trials is investigating the use of Avastin in over 50 tumor types (including colorectal, breast, non-small cell lung, brain, gastric, ovarian and others) and different settings (advanced or early stage disease).
About Avastin: Mode of Action

Avastin is an antibody that specifically binds and blocks the biological effects of VEGF (vascular endothelial growth factor). VEGF is the key driver of tumor angiogenesis – a fundamental process required for a tumor to grow and to spread (metastasise) to other parts of the body. Avastin’s precise mode of action allows it to be combined effectively with a broad range of chemotherapies and other anti-cancer treatments. Avastin helps to control tumor growth and extend survival with only a limited impact on the side effects of chemotherapy.
About Roche

Headquartered in Basel, Switzerland, Roche is a leader in research-focused healthcare with combined strengths in pharmaceuticals and diagnostics. Roche is the world’s largest biotech company with truly differentiated medicines in oncology, virology, inflammation, metabolism and CNS. Roche is also the world leader in in-vitro diagnostics, tissue-based cancer diagnostics and a pioneer in diabetes management. Roche’s personalised healthcare strategy aims at providing medicines and diagnostic tools that enable tangible improvements in the health, quality of life and survival of patients. In 2010, Roche had over 80’000 employees worldwide and invested over 9 billion Swiss francs in R&D. The Group posted sales of 47.5 billion Swiss francs. Genentech, United States, is a wholly owned member of the Roche Group. Roche has a majority stake in Chugai Pharmaceutical, Japan. For more information: www.roche.com.

All trademarks used or mentioned in this release are protected by law.

References:
1) WHO, IARC GLOBOCAN, Cancer Incidence and Mortality Worldwide in 2008

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In “Quality Measurement and System Change of Cancer Care Delivery,” published in the Regenstrief Conference supplement to the December 2011 issue of the journal Medical Care, investigators from the Regenstrief Institute and the Indiana University School of Medicine explore current cancer care quality measurement and discuss new ways to empower patients and promote system transformation to improve quality of care.

Cancer is the second leading cause of death after cardiovascular disease in the United States. However, the federal government and health care quality organizations have fewer reporting requirements for quality of cancer care than for treatment of many other diseases.

“As physicians consider treatment options for prostate, lung, breast and other cancers, they and the health care systems where they practice need to develop better tools to assess and measure the individual patient’s values and preferences,” said Regenstrief Institute Investigator David A. Haggstrom, M.D., a research scientist with the Center of Excellence on Implementing Evidence-Based Practice, Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service in Indianapolis. He is an assistant professor of medicine at the IU School of Medicine and a member of the Indiana University Melvin and Bren Simon Cancer Center.

Dr. Haggstrom says that quality medical care cannot subscribe to the one-size-fits-all theory. Questions must be asked, he says, to determine what cancer care is most appropriate for each individual. Does the patient want to be heavily involved in his medical decisions or would he prefer not to be overloaded by information? Does the patient want aggressive treatment from her medical team or does she prefer more conservative approaches?

“We have developed a roadmap which we believe provides a pathway to improve quality measurement and enhance consumer empowerment, thus improving delivery of cancer care,” Dr. Haggstrom said. “We propose important approaches that may change how we measure care for cancer patients, tackling such issues as racial disparities, wasteful overuse and patient-centeredness. We also propose applying new models of care to the problems of cancer, including accountable care to better coordinate the care delivered across multiple health care settings, as well as personal health records to deliver and collect medical information to and from patients. These new approaches may well positively disrupt how physicians and patients approach cancer care delivery.”
The paper was co-authored by Dr. Haggstrom and Regenstrief Institute Investigator Brad Doebbeling, M.D., M.Sc., an IU School of Medicine professor of medicine.
Indiana University School of Medicine

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The findings by the group of Research Professor Päivi Ojala (Institute of Biotechnology, University of Helsinki) demonstrates the first lymphatic-specific endothelial-to-mesenchymal transition (EndMT) induced by a human tumor virus. The virus-induced EndMT can contribute to development of KS by giving rise to infected, invasive cells, and providing the virus a permissive cellular microenvironment for efficient spread of the virus.

“This information can be used for developing targeted therapies to prevent or at least slow down the progression of KS in immunosuppressed patients”, Dr. Ojala says.

By developing a novel three-dimensional (3D) cell model to better mimic the in vivo microenvironment, the researchers show that KSHV induces transcriptional reprogramming of primary lymphatic endothelial cells (LEC) to mesenchymal cells via EndMT, a process implicated in promoting tumor growth and cell invasiveness. Mesenchymal markers were found co-distributed in the same cells with KSHV in primary KS tumor samples, suggesting that the 3D culture in this work succeeds in recapitulating the known heterogeneity of the cell types in KS tumors.

The results also reveal a key enzyme in cancer cell invasion, MT1-MMP, as a previously unrecognized signaling molecule downstream of Notch to induce EndMT. Moreover, the 3D KSHV-LEC transcriptome showed significant up-regulation of invasion related genes, that were found co-regulated in 3D KSHV-LECs and KS biopsies and suggesting that virus-induced EndMT may contribute to development of KS. The results further demonstrate that the 3D culture provides a permissive microenvironment for continuous viral replication and persistence, indicating the importance of virus-cell interactions for viral spread and thereby for oncogenesis.

“The unraveled molecular mechanisms can lead to identification of novel cellular targets for pharmacological control in virus-associated cancers”, Dr. Ojala says.

This work is a collaboration between the research teams headed by Kaisa Lehti, Kari Alitalo, Lauri Aaltonen, and Sampsa Hautaniemi (all from University of Helsinki), Chris Boshoff (UCL Cancer Institute, University College London) and Adam Grundhoff (Heinrich Pette Institute-Leibniz Institute for Experimental Virology). The project involves scientists from two Academy of Finland National Centre of Excellence Programs, the Translational Genome-Scale Biology and Cancer Biology.
University of Helsinki

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Using advanced imaging tools developed or used for the last decade at Johns Hopkins In-Vivo Cellular and Molecular Imaging Center (ICMIC), the team will search for innovative ways to detect cancers in their earliest stages inside cells, and for ways to stop or kill any of these cancer cells before the disease can spread to other tissues and organs.

“Our next round of studies are aimed at turning what we’ve shown to be feasible into clinical reality,” says cancer imaging researcher Zaver Bhujwalla, Ph.D., who will act as the principal investigator of the expanded initiative. The expansion is made possible with more than $8 million in new grants from the U.S. National Cancer Institute, a member of the National Institutes of Health. “By harnessing the very latest technology in noninvasive imaging using any single or combination imaging modality of MRI, CT, SPECT, PET, laser optics or ultrasound we expect to develop tests that detect cancer faster and earlier, distinguish spreading or metastatic tumors from dormant ones, and develop better and more tolerable chemotherapy drugs that only attack cancerous cells, leaving healthy cells alone,” she adds.

Bhujwalla says major advances in the last decade in genetic screening, blood testing and tumor biopsy have led to millions more people surviving cancer as a result of early diagnosis and careful treatment, especially chemotherapy and surgery to remove any cancerous tissue. But researchers say the next generation of cancer treatments will target the disease at the earliest, cellular level.

As director of the Johns Hopkins ICMIC, one of 10 such federally funded research centers in the United States, Bhujwalla will oversee more than 30 Johns Hopkins researchers, biostatisticians and lab technicians involved in the effort, advancing several existing and promising discoveries, as well as initiating new ones. Associate directors of the center will be Marty Pomper, M.D., Ph.D.; and Richard Wahl, M.D.

As a professor at the Johns Hopkins University School of Medicine Russell H. Morgan Department of Radiology and the School’s Kimmel Cancer Center, she also will serve as principal investigator in all ICMIC studies performed at Johns Hopkins.

For the new round of ICMIC experiments, Bhujwalla has teamed up with Pomper to evaluate image-guided therapy for prostate cancer, a process known as theranostic imaging, which combines diagnostic tools and therapy. Using a triple combination of SPECT and magnetic resonance scanning, along with optical or laser-guided imaging, the Hopkins team will attempt to identify cancerous prostate cells by homing in on a protein found solely on such cells’ outside layer. Once these so-called prostate-specific membrane antigens, or PSMAs, are found, researchers intend to use a chemically labeled drug, which can be tracked as it is absorbed into tumors, to kill the cancerous PSMA-labeled prostate cells, leaving healthy cells alone.

In another project, Richard Ambinder, M.D., Ph.D., is also using theranostic imaging in a study of 24 patients with Kaposi’s sarcoma, using PET scans, another type of noninvasive imaging, to guide a viral-activated drug, called bortezomib, to kill tumor cells.

Peter van Zijl, Ph.D., and Dmitri Artemov, Ph.D., will study magnetic resonance imaging techniques to detect the earliest possible metabolic and biological changes in breast cancer. Their goal is to find proteins or other small molecules that could serve as early warning signs of cancerous spread and, in combination with other genetic tests, identify women most at risk for cancer spread.

Kristine Glunde, Ph.D., and Xingde Li, Ph.D., are experimenting with laser imaging to analyze collagen fibers in breast cancer tumors. Studies have shown these fibers in distinct patterns in metastatic cancer, patterns that could be useful, in combination with other tests, to distinguish between women who need lymph node biopsy to see if their cancer is spreading, and those who do not.

Also funded by the latest grant will be a group of imaging pilot studies to measure the speed of skin cancer progression, led by Steven An, Ph.D.; to determine the amount of tumor shrinkage during pancreatic cancer treatment, led by Anirban Maitra, M.D., Ph.D.; to learn how cancer spreads to the lungs, led by Phuoc Tran, M.D., Ph.D.; and to evaluate novel treatments to prevent the spread of kidney cancer to the bones, led by Kristy Weber, M.D.

A portion of the grant will also be awarded to Mary-France Penet, Ph.D., for career development, under the direction of Peter Barker, Ph.D. Research infrastructure support in molecular oncology research methods will be co-directed by Venu Raman, Ph.D., and Elizabeth Jaffee, M.D.; in imaging and probe development, directed by Wahl and Artemov; and in biostatistics analysis, directed by Peng Huang, Ph.D.
source: Johns Hopkins Medicine

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Immune cells called regulatory T cells (“Tregs”) ensure that immune responses take place in a coordinated manner: They downregulate the dividing activity of helper T cells and reduce their production of immune mediators. “This happens through direct contact between regulatory cell and helper cell,” says Prof. Peter Krammer of DKFZ. “But we didn’t know yet what this contact actually causes in helper cells.” The researchers’ hypothesis was that the contact with the Tregs affects certain steps in the complex signaling cascade that leads to the activation of the helper T cells.

If the T cell receptor, a sensor molecule on the surface of helper cells, senses foreign or damaged protein molecules, this will trigger a cascade of biochemical activation reactions. At the end of this signaling cascade, genes that are required for an immune attack will be read in the nucleus of helper cells.

Jointly with colleagues from several German research institutes, Peter Krammer, Angelika Schmidt and co-workers have now compared the signaling cascades in helper cells with and without contact to Tregs. The immunologists found out that a short contact of the two types of cells in the culture dish is sufficient to suppress the helper cells. Following Treg contact, the typical release of calcium ions into the plasma of helper cells does not occur. As a result, two important transcription factors, NFkappaB and NFAT, do no longer function. They normally activate genes for immune mediators, thus alerting the immune system.

“The mode of action of Tregs is of great importance for cancer medicine. Many of our colleagues have shown in various types of cancer that Tregs can downregulate the immune response against tumors so that transformed cells escape the immune defense. This can contribute to the development and spread of cancer. We are therefore searching for ways to reactivate such suppressed helper cells,” said Krammer, explaining the goals of his work. For developing immune therapies against cancer it is also crucial to understand how Tregs work. The researchers are trying to prevent that immune cells which have been painstakingly activated against cancer in the culture dish are immediately suppressed again by Tregs.
Angelika Schmidt, Nina Oberle, Eva-Maria Weiß, Diana Vobis, Stefan Frischbutter, Ria Baumgrass, Christine S. Falk, Mathias Haag, Britta Brügger, Hongying Lin, Georg W. Mayr, Peter Reichardt, Matthias Gunzer, Elisabeth Suri-Payer and Peter H. Krammer: Human Regulatory T Cells Rapidly Suppress T Cell Receptor–Induced Ca2+, NF-?B and NFAT Signaling in Conventional T Cells. Science Signalling 2011, DOI: 10.1126/scisignal.2002179

source:Helmholtz Association of German Research Centres

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