September 2012 Irish Scientist Takes on Incurable Cancer with HRB Award

The Health Research Board (HRB) has announced it is to invest €11 million to build the capacity of research leadership in hospitals through its clinician scientist programme.

One of the clinician scientists chosen is Michael O’Dwyer, Professor of Haematology at NUI Galway and Consultant Haematologist, University Hospital Galway, who will head up a €1.7 million project.

Professor O’Dwyer aims to increase our understanding of the white blood cell cancer called Multiple Myeloma (MM). Despite major advances in treatment, MM remains incurable, and in patients with high-risk disease, who account for up to 25% of patients, life expectancy is less than three years.

MM is the second most common blood cancer in Ireland with approximately 250 new cases each year. It typically affects older individuals with two thirds of patients over 65 years of age and as the population ages the incidence and prevalence is increasing.

Throughout the lifetime of this programme Professor O’Dwyer, in collaboration with NUI Galway’s and Trinity College Dublin's Professor Frank Giles, will make emerging new therapeutics from all sources available to myeloma patients in early phase clinical trials through the HRB funded Clinical Research Facilities. Ultimately however, the goal is to translate their own laboratory findings to the clinic for the benefit of patients. 

“Our goal is to discover new ways to reduce the ability of the cancer cell to move to other sites within the body and identify new ways to make the cancerous cells more sensitive to chemotherapy drugs”, explains Professor O’Dwyer. “Ultimately, the laboratory findings will be applied to the clinic with the intention of improving treatment options for MM patients.”

According to Enda Connolly, Chief Executive of the HRB: “The best hospitals in the world have research at their core. The HRB Clinician Scientist Awards is part of our strategic aim to develop a culture of research and innovation in the health services, both for the benefit of patients and the Irish economy.”

Professor O’Dwyer will work with a network of scientific experts in NUI Galway and elsewhere around Ireland. Co-applicants on the grant are Professor Afshin Samali, Professor Lokesh Joshi and Professor Corrado Santocanale of NUI Galway, Professor Paul Browne of Trinity College Dublin and Dr Irene Ghobrial of the Dana Farber Cancer Institute, Boston. Additional academic collaborators include the Myeloma Ireland Consortium and the Mayo Clinic Scottsdale, Arizona as well as several industry partners.

The Science Bit

Professor O’Dwyer and his team plan to focus on two particular aspects of multiple myeloma biology. These are the vulnerability of plasma cells to excessive protein loads causing a phenomenon known as ‘ER stress’ and the role that glycosylation plays in the interaction of myeloma cells with the bone marrow microenvironment and vasculature, allowing them to traffic or metastasize from one location to another. 

Myeloma cells produce vast amounts of protein antibodies, which are assembled in the endoplasmic reticulum or ER. Excessive levels of protein are toxic, leading to ER stress and cell death.  Myeloma cells are adapted to deal with ER stress by increasing the activity of a protective pathway involving the IRE1 kinase. The presumption is that blocking this pathway should make myeloma cells more vulnerable to ER stress.  A major focus of this program is the evaluation of IRE1 inhibition as a new therapeutic option for multiple myeloma.  

Professor O’Dwyer and his team believe that the sugar coating or glycosylation status of myeloma cells plays an important role in trafficking, for example influencing the interaction between adhesion molecules called selectins and their ligands on myeloma cells. In this project they aim to explore the differences in glycosylation status between myeloma cells and their normal counterparts and their functional significance. They aim to identify novel new therapeutic targets, reducing the metastatic potential of myeloma cells and overcoming drug resistance.  They are also evaluating the myeloma activity of a novel selectin inhibitor.

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