MNC RESEARCH SUMMARY
Below is a summary of the research MNC has funded and conducted since 2011.
This study is the first of its kind to examine the needs of melanoma patients in Canada. Of the examined needs, needs for education and increased information were among the greatest reported. Not only were there a lack of information available, but participants suggested that electronic and print material is among the most favourable. Many participants as well need additional information about regularly screening. Specifically, it appears that individuals with less education (high school or less) have the highest need for educational and information resources. It is suggested that this sub-group of patients be particularly targeted specifically at time of diagnosis and throughout treatment. Although overall it appears the majority of needs are being met, it is apparent from this study that much more can be done to improve the care of melanoma patients in Canada.
- Angus Reid Public Opinion was commissioned by Hill and Knowlton to conduct a National Omnibus study on behalf of the Melanoma Network of Canada.
- The overall objective of the study is to provide research results which will help support the Networks’ Winter Sun Awareness campaign scheduled to launch in February 2011.
- The study examined Canadians’ views and behaviours related to wearing sunscreen in the winter and the summer months.
- A strong majority of Canadians know it is important to wear sun screen year round, but concern diminishes in the winter months. Few report that they always wear sun screen to protect themselves, regardless of the season.
- Messaging surrounding wearing sun screen in the winter can make a difference. A majority of Canadians report that if they knew that fresh snow reflects more UV rays than dry beach sand or the sea and that fresh snow can increase the amount of UV rays you are exposed to by up to 85%, they would be more likely to protect themselves from the effects of the sun.
| 2011 – 2016
Annette sat on the Board of Directors for 5 years.
The Canadian Cancer Research Alliance (CCRA) is an alliance of organizations that collectively fund most of the cancer research conducted in Canada – research that will lead to:
- better ways to prevent cancer
- diagnose cancer
- treat cancer and
- improve patient and survivor outcomes.
Part of the numerous research initiatives that we supported was the development of a national organization to promote independent clinical trials research for Cancers in Canada. The Canadian Cancer Clinical Trials Network (3CTN) was established in 2015. https://www.ccra-acrc.ca/
| 2012 – ONGOING
Annette Cyr has been the patient representative on the research and treatment committee since 2012. This groups helps to provide evidence-based recommendations on the treatment of melanoma and skin cancers in Ontario.
The Melanoma Disease Site Group (Melanoma DSG) produces evidence-based reports to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances. The titles of the reports produced to date by the DSG are listed on the website, with links to the PDF versions of those reports.
| 2013 – 2018
The major challenge in cancer therapy is to stop its metastasic progression, where the disease becomes resistant to most forms of therapeutic interventions. Understanding the metastatic mechanism is only beginning to emerge and is key to develop specific therapeutic interventions. Another complicating factor is the diversity of cancer cells within a tumor
(heterogeneity) that makes it difficult to optimize therapeutic regimen in individual patients. Recent evidence points to the existence in tumors of a small population of multi-potent therapy-resistant cancer stem cells (CSC), which survive treatment to regenerate tumors locally and produce metastases. It is therefore crucial to find novel therapies that can target these CSC in order to obtain truly effective anti-cancer treatments. Recent advances have uncovered novel ways to diagnose, follow and potentially treat cancer using a unique therapeutic target known as circulating tumors cells (CTCs). These cells are shed from the primary tumor or its metastatic sites and recapitulate many of the features of tumor heterogeneity. Importantly, CTC numbers follow closely the progression or regression of the disease. However, CTCs circulate in very low number making it difficult to study them. Recently, we have developed a novel approach to isolate CTCs in large numbers from a series ofbreast cancer patients by a procedure called aphaeresis and we have banked these live cells and expanded the frozen aliquots in serum free conditions in vitro in both adherent and non-adherent (mammospheres) cultures. We also characterized the phenotype of these cultures using classical markers of breast CSC. We now plan to apply the same methodology to patients diagnosed with metastatic malignant melanoma. We will aim to detect unique CTC-specific molecular signatures that can aid in the prognosis and the tendency of progression of the disease. We will also test the CSCs response to a variety of chemotherapeutic agents in vitro in view of developing personalized therapeutic regimen. By knowing early on, following diagnosis, the sensitivity of CSC to chemotherapeutic regimen, we hope to maximize therapeutic efficiency in the early stage of therapeutic intervention and modulate these regimen overtime. In addition, we hope to detect unique molecular signatures of CSC that can be used in the near future to develop targeted molecular therapies, overcome drug resistance and specifically target the metastatic CSC.
- Published – ‘Detection methods of circulating tumor cells in cutaneous melanoma: A systematic review’ Critical Reviews in Oncology/Hematology Stefan Rodica, Catalin Mihalcioiub, Ramy R. Salehb,∗aDivision of Biology, McGill University, Montreal, CanadabDivision of Medical Oncology, McGill University Health Centre, Montreal, Canada Accepted 14 January 2014Grant total: $225 through MNC and CIHRResearch is ongoing
| 2013 – 2014
Lymphedema booklet and reference tool developed and published and is used as a primary resource document for uveal melanoma patients at major cancer treatment centres.
| 2013 – 2014
‘A Pilot Study Examining the Development of an Evidence-Based Patient Booklet about Lymphedema for Newly Diagnosed Melanoma Patients’ was conducted by intern medical student Annie Liu. This study examines the development and evaluation of an evidence-based patient booklet about lymphedema for newly diagnosed melanoma patients. Its purpose is to uncover any gaps in lymphedema resource tools for melanoma patients, develop and design an appropriate tool and evaluate its design in order to ensure quality in the product.
| 2013 – 2015
MNC research project ‘Assessing patient and caregiver satisfaction with the Melanoma Network of Canada: A Program Evaluation’ conducted by Melanie Kalbfleisch (now Dr.) into the support programs at MNC and subsequently published a study pointing to the need for ongoing psychosocial support.
- Educational resources should be aimed at programs to help with financial stress (drug costs and homecare)
- Patients and caregivers feel the need for more educational resources and social support networks
There were some respondents who were happy with the services they receive and said they did not need other services
Leftright Strategic Learning Consultants conducted research into existing programs for youth education on sun safety, prior to launching into program design. Research goals were to identify:
- Current or recent sun safety programs that have been launched by other organizations, primarily in Canada, US, England and Australia
- What if anything from current programs might be leveraged
- Pitfalls to avoid and best practices to mirror or incorporate
- Key messages to different ages and stages of children
- Different approaches to raise awareness of sun safety with different ages of children, youth, and teens
- How to utilize the Canadian education system as a delivery channel for the message
- Current and best practices in marketing and communications strategies for sun safety or similar health awareness campaigns
- How to leverage the digital space
Current State of Programs included:
– Literature review: 53 Articles published between 1995-2012; several unpublished reports
– Four 45 minute Interviews (reps from Canada, US and Australia)
– 14 comparative programs which incorporated educational/awareness materials
- Market Research included:
– 25 websites from countries around the world that were specific to sun safety
– 15+ sun-safety specific apps; 4 games about sun safety
– 30+ different videos on the subject of sun safety
– 30 web sites not specific to sun safety but were otherwise specific to our demographic
– University Of Bristol report specific to sun safety and social media
– 20+ sites on the subject of marketing to youth: digital marketing, health-related marketing to
youth, digital campaigns for awareness and behaviour change, general and specific trends
- Education System, Children’s Camps included:
– Analysis of curriculum from each of the provinces and territories in Canada
– Outreach to trustees, principals, Health and Mental Wellness Committee (TDSB)
– Review of Healthy Schools Programs
– 4 Key informant interviews (Toronto and Ontario Eco Schools and Ontario Camps Association)
– Literature review
- Because of rich existing educational materials, do not build from scratch. Consider:– Customization– Advocate use of existing and point to them– Invest effort in ensuring use at schools– Repackage in format/structure appealing to teachers (if appropriate)
- Look for and create MNC niche elsewhere
– Digital space for teens; camps, after school programmes, school wide initiatives
- Develop long-term plan to influence and change school approaches.
– Grass roots change agents and advocates (teachers, principal, school advisory councils)
– Pilot small with a few schools
– Growth plan and endorsement from superintendent; steering committee with
representation and advocates from each school
- Short term: leverage, leverage, leverage
– Shade Program
– Partner offers – OCA, Public Health, CDA
| 2014 – 2015
‘Assessing the need for resources for patients with uveal melanoma’ was conducted by intern medical student Anthony Mak & co investigator, Annette Cyr. Uveal melanoma (UM) is a rare, malignant tumour of melanocytes in the eye that affects the uveal tract. Each year, approximately 150 patients in Canada are diagnosed with UM and are treated at the Princess Margaret Cancer Centre (PMCC), Canada’s leader in UM treatment and research. Presently, there lacks information/education resources and support services for patients with UM in Canada. We at the Melanoma Network of Canada, in partnership with the PMCC, conducted a research study to assess the need for support services and information resources for patients with UM. Our qualitative research study consisted of semi-structured telephone interviews to determine patient perspectives, experiences and opinions regarding information and services that would be benefit and relevant to patients with UM.
- The Ontario Education System
• Non-school programs for children: Camps and After-School Programs
Annette has been on the Steering Committee, the Strategy Committee and the Disease Site committee for increasing the number of melanoma clinical trials since the network started.
The Canadian Cancer Clinical Trials Network (3CTN) is a pan-Canadian initiative to improve the efficiency and quality of clinical trials in Canada. 3CTN will provide support and coordination for a network of teams at cancer treatment centres and hospitals. With regional participation, 3CTN will enable sites to increase their capacity and
| 2015 – 2016 FUNDING PROVIDED
Vemurafinib is the first targeted agent to show improved overall survival in BRAF mutant metastatic melanoma patients. The
development of resistence to vemurafinib is however invariable limiting the long term use of this agent. Immunotherapies such as ipimulimab have additionally shown durable responses in 20% of patients. Evaluation of tumour tissues has
suggested that increase in number of “tumour infiltrating lymphocytes” (TILs) after treatment with ipimulimab correlated with patients’ clinical response. The role of TILs in patients receiving BRAF inhibitors such as vemurafenib, however, has not been widely studied and it is unknown how critical the immune response is for patients to respond to vemurafenib. Better
understanding of the role of TILs and responses seen in vemurafinb treated patients may lead to new therapeutic strategies to optimize the current treatment paradigm.
| 2015 – 2017
MNC is a member – Annette has been ongoing active participant
Participated in research and development of new sun safety wording and guidelines and fact sheets
Changes included: New consistent sun safety wording; eye protection, so safe tan; peak UV index times, positioning on vitamin D; and adopting SPF 30 as minimum
Overall, the evidence for the effectiveness of sun protection education interventions was strong in terms of knowledge, moderate in terms of changing attitudes and behavioural change, and inadequate in terms of skin changes.
| 2017 ONGOING
“In patients diagnosed with melanoma, is there a significant reduction in patient-reported anxiety or improvement in mood associated with their diagnosis following participation in the Within Reach peer-to-peer support program?” In addition, we will assess the patient’s satisfaction with the peer support program.
Pam Ohashi, a Senior Researcher at PMH, has applied for an NCE grant to focus on autoimmunity. Part of the grant is to look at therapeutic autoimmunity such as irAEs. We (MNC) serve as an advisor for this grant in our capacity as a patient advocate. They are proposing to build a Network Centre of Excellence on Immunomodulation, including autoimmunity and cancer immunity.
Research grant pending.
ISSN: 0160-9513 (Print) 1540-9481 (Online) Journal homepage: http://www.tandfonline.com/loi/wswg20
Results of this research have demonstrated high participant satisfaction with an in-person support group for melanoma patients and their caregivers. We have established a support group that is feasible in terms of program structure, session format, and sustainability as a volunteer-run group. Similar non-profit organizations may benefit from using the strategies outlined in this research to provide a low-cost support group option for their population of interest. Future research should explore the psychosocial impacts of participation in the Melanoma Patient Exchange program for participants, alternative methods, such as incorporation of technology, to increase the number of participants attending each session.
| 2018 ONGOING
Clinical problem that will be addressed: Immune checkpoint inhibitor antibodies, which include anti-CTLA4 (ipilimumab) and anti-PD1 (nivolumab and pembrolizumab), have produced durable survival benefits in 20-50% of melanoma patients. However, these therapies can produce severe immune-related toxicity that are life-threatening. Currently, the factors that inform on patient response to immune therapy are unclear. Furthermore, it is still unclear how BRAF and MEK targeted therapies modulate the response to checkpoint inhibitors in melanoma. This information is critical to reduce treatment costs by providing the most effective therapies for patients and to limit costly hospitalization due to treatment-related adverse events.
Deliverables: We will generate a multi-dimensional treatment response algorithm to predict outcomes of immune and targeted therapy in melanoma.
Socio-economic benefits: The economic burden of cutaneous melanoma estimated by the Canadian Cancer Society is approximately $450 million per year. Costs to manage treatment-related grade 3/4 adverse events (AEs) are significant, ranging from $200-10,000 per AE, necessitating the development of improved biomarker-based decision algorithms to inform on patient response. Biomarkers we develop from blood-based biopsies will spare patients with melanoma repeated expensive and sometimes inaccessible tumor biopsies and decrease the reliance on CT scans, which often have long wait times and potential for harmful radiation exposure.
Research grant pending.
Deliverables: Researchers will generate a multi-dimensional treatment response algorithm to predict outcomes of immune and targeted therapy in melanoma.
About 50% of cutaneous melanomas harbor a mutation in BRAF, with the V600E mutation being the most common. Responses to mutated BRAF are transient, and development of resistance to inhibitors often leads to disease recurrence.
Our team has published several key papers showing that a pair of proteins, termed Mnk1 and Mnk2, cause tumor cells to become metastatic. With this knowledge, we teamed up with the pharmaceutical industry to develop a novel orally bioavailable therapeutic inhibitor of Mnk1 and Mnk2, which we named SEL201. In October 2017, we published that the drug SEL201 could be used to block the aggressiveness of acral melanoma. We are encouraged by the pre-clinical data obtained with SEL201, as patients with acral melanomas are often unresponsive to frontline therapies. Moreover, our recent data with SEL201, suggest that inhibition of Mnk1 and Mnk2 may hold promise in combination with inhibitors of BRAFV600E and MEK in cutaneous melanomas harboring BRAF or NRAS mutations.
AIM 1: Test SEL201 as monotherapy and in combination with inhibitors of BRAFV600E and MEK in pre-clinical models of melanoma.
Expected outcome (Aim 1): Using our pre-clinical mouse models of cutaneous melanoma we are well poised to identify novel combinations of drugs to (1) improve the efficacy of existing anti-tumor agents, and (2) delay or block therapeutic resistance.
AIM 2: Use state of the art genome editing technology to identify novel targetable survival and metastatic pathways in melanoma.
Expected outcome (Aim 2): A major strength of this aim is that our genome editing approach has an emphasis on cellular targets for which there are FDA approved drugs. Therefore, any target that we identify as being essential for metastasis, for example, can quickly be tested in our pre-clinical models of melanoma.
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