More than half of all patients with ovarian cancer experience recurrent disease and will eventually fail to respond to chemotherapy. The failure of chemotherapy is usually due to the development of resistance to the two main classes of chemotherapy agents used to fight it – platinating agents and taxanes. Now, a study reported in the open-access Journal of Ovarian Research provides novel information that further adds to clinicians’ understanding of the mechanisms involved in the development of resistance to dual-agent chemotherapy.

It was not known whether mechanisms of resistance to dual-agent chemotherapy are a combination of single-agent resistance responses or if novel mechanisms arise as a result of combined platinating agent/taxane therapy. Dr. Carita Lannér and her team, comprised of researchers from the Northern Ontario School of Medicine (NOSM), Health Sciences North (HSN), and Laurentian University, provide evidence to suggest that the latter is true: novel and different changes occur to cause resistance to the dual combination of agents.

Ovarian cancer is the most lethal gynecological cancer, with a five-year mortality rate of over 50%. A significant contributing factor to the high mortality rate is the development of resistance to chemotherapy regimens. The differences in mode of action and mechanisms of resistance for platinating agents and taxanes are taken advantage of in dual-agent chemotherapy of advanced cancer. Used together, they achieve increased efficacy and progression-free survival in patients. However, combined resistance to both agents may occur, and is more difficult to overcome than single-agent resistance.

Dr. Lannér and colleagues set out to investigate if the development of dual agent resistance invokes different mechanisms or is a combination of the mechanisms of resistance that arise upon exposure to single agents. To do this, they developed a set of isogenic ovarian cancer cell lines resistant to (1) the platinating agent carboplatin, (2) the taxane docetaxel, or (3) a combination of carboplatin and docetaxel. They analyzed changes in gene expression associated with the specified drug resistance in each cell line using microarray analysis.

The team compared the three resistant cell lines to identify shared and different changes in gene expression amongst all three treatments. The analysis showed that the establishment of carboplatin and docetaxel resistance did not share many changes in gene expression. Most significantly, dual-agent resistance appeared to develop from mostly unique changes in gene expression, different from both single carboplatin and docetaxel resistance in the set of isogenic cell lines studied.

Lead author Dr. Lannér commented, “These results demonstrate that combined drug resistance is not just a combination of changes present in single agent-resistant cells but contains different and new changes. The dual carboplatin-docetaxel resistant cell line will facilitate further investigation into mechanisms underlying the development of dual drug resistance in ovarian cancer.”

Research Background Information

Research Group:
Stephen R. Armstrong, Rashmi Narendrula, Dr. Baoqing Guo, Dr. Amadeo M. Parissenti, Katherine L. McCallum, Stephanie Cull and Dr. Carita Lannér

Exemplary Learners, Faculty and Preceptors Recognized by NOSM Board 

The Board of Directors of the Northern Ontario School of Medicine (NOSM) held a face-to-face meeting in Sudbury on November 29 and 30, 2012.

On the first day of the two-day meeting, Board members were provided a tour of the Shkagamik-Kwe Health Centre led by the Centre’s Executive Director and past NOSM Board member, Ms. Angela Recollet and Centre staff members. Board members were treated to a delicious traditional lunch, and heard inspirational stories from health professionals working at the Centre. The visit concluded with a presentation of a Shkagamik-Kwe Health Centre healing blanket to NOSM.

In the afternoon, several of NOSM’s senior leaders led interactive sessions with the Board about the School’s Advancement objectives, how the Ministry of Health and Long-Term Care funds NOSM, and the challenges of Postgraduate Medical Education in Northern Ontario.

Later that evening at the Board dinner, Awards of Excellence were presented to learners, faculty and preceptors by Dr. Laura Piccinin, Assistant Dean of Learner Affairs and Dr. David Marsh, Associate Dean of Community Engagement. Learners receiving awards included Ms. Kendra Komsa and Mr. Kyle Lee (MD students), and Ms. Danielle Brubacher and Ms. Kaitlin Cobean (Dietetic Interns). Drs. Jean Anawati and David Clarke were the recipients of faculty and preceptor awards. Ms. Gayle Adams-Carpino, Interprofessional Education Program Lead and faculty member, received the newly created NICHE (Northern Interprofessional Collaborative for Health Education) Award of Excellence in Innovation and Leadership in Interprofessional Health Education.

On the second day of the meeting, the Board participated in discussions about stakeholder consultation and governance policies, and received a summary of this year’s most exciting international conference for health professional education, Rendez-Vous 2012. More than 850 delegates from nearly fifty countries and six continents-including 486 delegates from North America, 124 delegates from Africa, 100 delegates from Australia, 80 delegates from Asia, 51 delegates from Europe, and 37 delegates from South America-came to this stimulating conference, hosted by NOSM in October, to share experiences, consider new ideas, and learn from each other. (More information about Rendez-Vous 2012 can be found at www.rendez-vous2012.ca.)

At an impressive keynote address given over lunch, Board members heard from Dr. Terrance Galvin, the Founding Director of Laurentian Architecture Laurentienne (LAL). Dr. Galvin spoke about the consultative processes and cultural and architectural inspirations that have informed the planning of the first new school of architecture in Canada to be launched in over 40 years. LAL, located in the heart of Sudbury’s downtown, will welcome its first students in September 2013.

At the formal Board meeting, members received reports from the Finance and Audit, Quality Monitoring, Executive, Governance, and Advancement committees. The Board also received reports from the School’s Francophone and Aboriginal Reference Groups.

The Board of Directors approved a Financial Report from the Finance and Audit Committee for the six-month period ending October 31, 2012.

Mr. Dominic Giroux, Chair of the Northern Ontario School of Medicine’s Board of Directors and President of Laurentian University, noted that the two-day meeting accomplished several important objectives. “Group cohesion and opportunities for interactive sessions and discussions are enhanced when Board members are able to meet in person. This two-day meeting, which included thought-provoking presentations, and celebrated the outstanding contribution of NOSM’s learners, faculty and preceptors, was a great success,” he said.

The Northern Ontario School of Medicine’s next Board of Directors meeting is scheduled to occur on March 20, 2013.

For a complete list of Board members, please visit our website at www.nosm.ca .

Contact: 

news@nosm.ca

On Friday, October 12, to Saturday, October 13, 2012, delegates from the Rendez-Vous 2012 world conference will visit various community organizations and cultural sites across Thunder Bay and area, through a program called Portage Express.

Ranging from Aboriginal and Francophone culture, interactive historical displays and treks in the wilderness to health education, research and technology, Northern search and rescue, and on through hospital-centred care, each of these journeys will introduce delegates from around the world to life in our North. More than 30 locations will receive Rendez-Vous 2012 delegates, with some locations such as Thunder Bay Regional Health Sciences Centre (TBRHSC) and St. Joseph’s Care Group welcoming delegates to various departments across the organization.

“The Northern Ontario School of Medicine is known for its unique partnerships with community members across Northern Ontario,” explained Dr. Roger Strasser, NOSM Dean. “Understanding the social, cultural and health determinants of Northern Ontario is an integral part of socially accountable health professional education at NOSM. Community sites participating in the Portage Express will showcase the cultural fabric and services of the region that we serve.”

NOSM’s community partners are integral to our model of distributed community-engaged medical learning and research. Portage Express is an opportunity to showcase partnerships like the one between NOSM and the community of Thunder Bay.”

Conference delegates will have the opportunity to visit sites that include, but are not limited to: Alpha Court, Thunder Oak Cheese Farm, Gammondale Farm, Canadian Cancer Society, Canadian National Institute for the Blind, Fort William Historical Park, The Salvation Army Community and Residential Services, Thunder Bay Regional Health Sciences Centre, and the Waabi-ma’iingan (Grey Wolf) Traditional Teaching Lodge.  For a full list of organizations participating in the Portage Express, please visit www.rendez-vous2012.ca/community-visits.