Those who have contributed in any way to the Emer Casey Foundation’s inspiring efforts to combat ovarian/uterine cancer, particularly through early detection, can be immensely proud of the results generated by their efforts.  Immediately following the 2010 Emer Case 10k on May 23rd, Professor John O’Leary of the Institute of Molecular Medicine at Trinity College Dublin addressed the participants at the assembly point in Pobalscoil na Trionoide. His message measured that, in truth, breakthroughs of immense importance, magnified by the foundation’s links with various international medical research centres, continue to emerge.

Professor O’Leary leads the DISCOVARY consortium, which is composed of researchers from several institutions who undertake world-class research into ovarian and endometrial cancer. DISCOVARY’s primary goal is to understand these cancers, develop new early detection methods and design novel treatment options.

The Emer Casey Foundation sponsors three Phd fellowships for the consortium and their focus lies in the areas of chemoresistance, cancer stem cells, circulating tumour cells and the body’s immune response to cancer. They are Mairead Murphy, Lynda McEvoy and Brendan French and they also addressed the gathering on recent progress in their individual projects.

The consortium’s overall profile and its considerable achievements can be viewed online at www.emercaseyfoundation.com Meanwhile Professor O’Leary and his workers addressed advances made in the past twelve months.

A year of great progress

The professor began by deliberating on “some very important discoveries and breakthroughs” over the year. He described how an “inflammatory pathway” involved with ovarian cancer had been discovered. The pathway is compiled of a protein called TLR4 and its accompanying adaptor molecule, MyD88. The terms are technical but the research indicated that, “some of the treatments we presently use for people with ovarian cancer may inadvertently activate this pathway,” which suggested that such cancer cells that express TLR4 and MyD88 are more likely to be chemoresistant and will behave like cancer stem cells. “That’s a major statement,” he stressed, adding that, “hospitals involved with the DISCOVARY consortium, are asking their ethics boards if they can start testing for these particular genes or proteins as part of managing the treatment with ovarian cancer patients.”

Professor O’Leary also told how the fellows are collaborating with the Royal College of Surgeons, Ireland (RCSI) and Dublin City University (DCU) in examining the role of platelets in cancer cell metastasis. The process, called ‘platelet cloaking,’ is “a major step forward in understanding how tumour cells spread in the blood stream.”

The professor proceeded that the consortium has “engaged a second group in UCD that have discovered a new protein in ovarian cancer called Mad-2. The presence of this “really bad protein” in ovarian cancer sufferers signified a much bleaker outlook. Thanks directly to the Emer Casey Foundation, an important paper on this issue was expected to be published in the coming months.

The three students are also commencing research in tandem with colleagues at the Dana Faber Cancer Institute, Harvard University, USA, who approached them and asked for collaboration. This work “will focus on deep analysis of the role of MyD88 in tumour cell chemotherapeutic responses and to carry out live cell imaging of cancer platelet interactions.” This collaboration is seen as creating “a dynamic two-way interaction between scientists on both sides of the Atlantic.”

The three students/Fellows funded to the consortium by the Emer Casey Foundation also addressed the gathering, with each indicating their specific area of research and offering a brief synopsis of their progress. In this instance particularly, much of the terminology used is technical and, frankly, unlikely to convey its immense significance if represented here in full. Briefly, the speakers were represented thus:

1)  Lynda McEvoy: deals with “Developing Novel Therapeutic  approaches in Chemoresistant Ovarian Cancer Paitents.’

Lynda aims to help formulate new ovarian cancer treatments and improve current ones. She is investigating why some ovarian cancer patients, having responded well to initial chemotherapy before relapsing and becoming resistant to treatment. She refers to one possible cause as tumour hypoxia, which is another way of saying ‘a reduced level of oxygen in the tumour.’ She has investigated the effect of hypoxia on the standard treatment for ovarian cancer, by subjecting the drugs combination cisplatin and taxane  to various conditions. Her findings “may provide novel targets for new therapeutic drugs,” she says. Her future plans include collaboration with DCU in examining the response of cells taken from a patient’s tumour to different concentrations of chemotherapy drugs and different concentrations of oxygen in order to tailor a chemotherapy regime that is suited to a patient’s particular tumour.”

2. Mairead Murphy: deals with ‘Developing and Validating  Diagnostic Serum Based Biomarker Panels in Ovarian Cancer.’

Mairead’s work aims to identify biomarkers associated with ovarian cancer. A biomarker is a substance that provides information about underlying processes within the body. To determine biomarkers she has profiled antibody patterns in the serum of ovarian cancer patients and then compared them to those of healthy volunteers. (Antibodies are proteins found in the blood or body fluid and make up the core of the immune system.)

She has identified patterns of some previously identified biomarkers and also potential biomarkers that may be used to detect various ovarian diseases, including cancer. Her task is to define the best possible treatment for ovarian cancer by distinguishing between different ovarian diseases. Through the presence of one sort of antibody (immunoglobulin G) in the blood she can probe the immune repertoire of patients over a period of up to 10 years and thus acquire information on cancer progression. A second type of antibody (immunoglobulin M) may provide an earlier assessment however and the two combined “should provide a greater insight into cancer progression and patient immune response,” she concludes.

3. Brendan French: deals with the ‘Isolation Characterisation and  Silencing of Ovarian Cancer Stem Cells.’

Brendan, the latest recruit to the fellowship thanks to the public’s financial support, is studying the hypothesis whereby growth and repair of cancer tissue –as with normal tissue- is carried out by stem cells (CSCs). Cancer stem cells are thought to be resistant to therapy and capable of replenishing tumors post-treatment.

His project aims to isolate supposed CSCs from ovarian cancer. Once isolated, it is intended to validate these putative CSCs through various hallmarks associated with stem cells, such as chemoresistance, resistance to low oxygen conditions, etc. Once validated as stem cells the project will endeavour to discover what makes the CSC’s different to general cancer cells with the intention of identifying ways to differentiate/kill them and so make enhance the success of ovarian cancer treatment. This work is in its early stages but so far has identified and isolated one population of cancer stem cells from one line of ovarian cancer cells.

Summary

In summary, the Emer Casey Foundation is sponsoring ovarian cancer research in the areas of chemoresistance, cancer stem cells, circulating tumour cells and the body’s immune response to cancer. The scientists have already identified a panel of proteins that can be found in the blood of ovarian cancer patients and have developed a near-patent testing device to assess a patient’s response to chemotherapy. They are mow working on new ways to isolate circulating tumour cells in a patient’s blood.

War

Back on the support trenches, so to speak, of the war against ovarian cancer, Professor O’Leary had a stark but inspiring message for the troops assembled before him in Pobalscoil na Trionoide. “One in three of you here will get cancer and two in three of you will work or live with someone who will get it,” he said. Yet, “ordinary people are leading the fight against the ‘silent killer,’” he stressed. “You are contributing to a body of knowledge searching to establish early detection methods and striving to understand how these tumours can be treated.” He proceeded, “ Your money is making a major impact on the progress of Irish scientists that is being internationally recognized. That is why the running, walking and weeping you did today is so very important. I thank you from the bottom of my heart.”