A $1.9 million grant recently awarded to BC Cancer Agency researchers by the Canadian Breast Cancer Research Alliance will help scientists translate discoveries about breast cancer into better treatment.
Approximately 5,400 women in Canada will die from breast cancer this year. Despite advances in the treatment of early and advanced breast cancer, further advances in treatment are required to improve the outcome of women with this disease. As the benefits of existing treatments reach their potential, the focus of research is shifting to attack specific molecular targets involved in the cause or progression of breast cancer.
The overall project, Translating target discovery into better health outcomes for women with breast cancer, brings four connected breast cancer research projects together. Each project is geared toward a common goal: identifying why certain breast cancers behave the way they do at the molecular level, and how this knowledge can help clinicians plan treatment methods for maximum benefit. As well as assessing specific tumour markers, this project creates a framework for identifying and validating future potential targets.
"This grant is exciting as it is true translational research. We are linking scientists and clinicians in order to try and accelerate the speed at which we turn basic science into clinical applications," explains Dr. Karen Gelmon, principal investigator and team leader with Dr. David Huntsman, both from the BC Cancer Agency.
The principal investigators of each individual project are:
- Dr. Marcel Bally & Dr. Shoukat Dedhar (BC Cancer Agency)
- Dr. Brian Norris (BC Cancer Agency) & Dr. Blake Gilks (BC Cancer Agency, Vancouver Hospital)
- Dr. Stephen Chia & Dr. Karen Gelmon (BC Cancer Agency)
- Dr. Jonathan Lee (Hamilton Regional Cancer Centre)
(A summary of each project is attached)
Other researchers and co-investigators integral to the program include: Dr. Michael Roberge (UBC); Dr. Cal Roskelly (UBC); Dr. Afshin Raouf (BC Cancer Agency); Dr. Connie Eaves (BC Cancer Agency); Dr. Dawn Waterhouse (BC Cancer Agency); Dr. Ivo Olivotto (BC Cancer Agency); Dr. Chris Bajdick (BC Cancer Agency); Dr. Sandy Dunn (BC Children's Hospital); Sr. Stefan Gluck (Tom Baker Cancer Centre); and Dr. Peter Ravdin (University of San Antonio).
While each of the researchers has a specific and unique focus, they will be sharing information and findings for the common goal of creating individualized diagnostic tests and therapies for women with breast cancer.
One of the strengths in matching the laboratory to the clinic is the participation of patient advocates, who help keep the team aware and focused on the treatment and ethical needs of women with breast cancer.
Research such as this has allowed Dodie Katzenstein, a breast cancer patient with a very aggressive form of the disease, to enjoy a longer life than she first thought would be possible. Recent research into biomarkers which distinguish how different tumours react to different therapies showed that her particular cancer might respond well to a drug called Herceptin, which was the first of this type of therapies targeted to tumours at the molecular level. While not a cure, it has improved Ms. Katzenstein's quality of life, and extended her time.
She (along with another patient advocate Judy Caldwell) had provided feedback to the team while they developed their grant application and will continue to be involved as the research progresses. It is hoped that this will help apply discoveries at the molecular level quickly into new forms of diagnosis and treatment for women with breast cancer.
In comments prepared as part of the proposal process, she explained her support:
"I realize that the research funded through this grant—no matter how accelerated— probably will not change the outcome of my own breast cancer story," says Ms. Katzenstein. "But I know that this important work will benefit other women now living with breast cancer, and the thousands who will be diagnosed in coming years. This research program also gives me hope that a better understanding of this complex disease will offer my daughter and the women of her generation the best chance for a long and healthy life."
Investigators plan to take their discoveries in the lab to the clinic as quickly as possible, through Phase I and II clinical trials.
The Canadian Breast Cancer Research Alliance is a collaboration of the Canadian Breast Cancer Foundation, the Canadian Breast Cancer Network, Canadian Cancer Society, Health Canada, the Canadian Institutes of Health Research, and the National Cancer Institute of Canada.
The BC Cancer Agency, a part of the Provincial Health Services Authority, is committed to reducing the incidence of cancer, reducing the mortality from cancer, and improving the quality of life of those living with cancer. It provides a comprehensive cancer control program for the people of British Columbia by working with community partners to deliver a range of oncology services, including prevention, early detection, diagnosis and treatment, research, education, supportive care, rehabilitation and palliative care. The BC Cancer Research Centre conducts research into the causes and cures for cancer.
For more information, or to arrange an interview, please contact:
Nicole Adams
BC Cancer Agency
(604) 877-6272
Summary of Projects
Translating target discovery into better health outcomes for women with breast cancer
Principal Investigators: Dr. Karen Gelmon, MD – BC Cancer Agency; Dr. David Huntsman, MD - BC Cancer Agency
Breast cancer is currently divided into broad groups that indicate sensitivity to estrogen and HER2/neu expression levels. Today, this classification system appears overly simplistic and both recurrence and survival rates reflect inadequacies of our current staging and treatments. This program will test four new genetic factors to determine whether they can be used to better predict which breast cancers will recur and which will respond to therapy. We will develop new drugs to target these genetic factors and believe that such targeted treatments will prove more effective and less toxic than current therapies. Through these studies on specific genetic factors we hope to improve the diagnosis and care of breast cancer patients. However, more importantly, by working as a multi-disciplinary team, we will develop and validate an accelerated approach for the translation of future genetic discoveries into improved outcomes for women with breast cancer.
Preclinical studies designed to rapidly establish the utility of integrin linked kinase inhibition as an approach to treating breast cancer
Principal Investigators: Marcel Bally, PhD – BC Cancer Agency; Shoukat Dedhar, PhD – BC Cancer Agency
There are two important features of this grant proposal, a proposal designed to test whether a signal generated inside breast cancer cells can be inhibited such that the cells will be less likely to divide and may become more sensitive to standard therapies used to treat breast cancer. The first concerns the collaboration developed between the scientists participating in this research proposal. This collaboration combines the expertise of a scientist, Dr. S. Dedhar, which discovered the signal that is being targeted with academic based drug development experts. In addition, a clinician, Dr. Karen Gelmon will play the lead role in coordinating the research such that its relevance to patients with breast cancer is kept foremost in mind. The second feature that is uniquely illustrated by the proposed research concerns the common goal of wanting to determine whether inhibition of the targeted signal will be useful in the management of women with breast cancer. This aspect of this work will determine whether the signal is diagnostically or prognostically important as well as determine how drugs targeting this signal will be used to achieve optimal therapeutic benefits.
A comprehensive strategy for the integration of novel biomarkers into early breast cancer care
Principal Investigator: Dr. Brian Norris, MD – BC Cancer Agency; Dr. Blake Gilks, BC Cancer Agency, Vancouver Hospital
The primary objective of this study is to advance early breast cancer care by using biomarkers to better discriminate risk and/or determine the likelihood of response to taxane chemotherapy. Prognostic factors help determine the risk of spread or death from a cancer. Predictive factors determine the chance of response to drug therapy. Molecular/genetic alterations that drive change within a breast cancer cell are potential biomarkers. Three such potential biomarkers (EMSY, EEF1A2 and pILK) will be tested to see if they better predict recurrence risk for node negative patients, compared to standard risk assessment, with the use of a computer program known as ADJUVANT! The biomarker EEF1A2 also helps break up a cellular structure called microtubules. Microtubules are targets of chemotherapy drugs known as taxanes and cells with increased EEF1A2 might be less sensitive to a taxane. We will test if EEF1A2 is a marker of response to taxane chemotherapy.
A phase I pharmacokinetic and pharmcodynamic study of weekly and twice weekly OSI-774
Principal Investigator: Dr. Stephen Chia, MD - BC Cancer Agency; Dr. Karen Gelmon, MD – BC Cancer Agency
Approximately 5,400 women in Canada will die from breast cancer in 2002. Despite advances in the treatment of early and advanced breast cancer, further advances in treatment are required to improve the outcome of women with this disease. As the benefits of chemotherapy and hormonal therapy has likely reached its maximal potential, the focus now shifts to attacking specific targets involved in the cause or progression of breast cancer. One such target is the epidermal growth factor receptor (EGFR). Specific inhibitors of EGFR, such as OSI-774, has shown limited activity given on its current schedule of once daily oral dosing in advanced breast cancer. This study aims to determine the appropriate dose of OSI-774 given on different schedules, once weekly and twice weekly, in advanced cancer patients in hopes of improving the activity of this class of compounds alone and in combination with chemotherapy or hormonal therapy in breast cancer.
The role of protein elongation factor EEF1A2 in breast cancer
Principal investigator: Jonathan Lee, PhD – Hamilton Regional Cancer Centre
The development and progression of breast cancer is accompanied by changes in the DNA of the tumour. It is believed that these DNA alterations cause normal breast cells to become cancerous. The identification of DNA changes between normal and cancerous breast tissue is critically important in our ability to diagnose, treat and ultimately cure breast cancer. Common DNA changes that occur in breast cancer are deletions, where normal DNA is lost,and amplifications, where normal DNA is increased in number. The focus of this grant is the EEF1A2 gene. Previous work has shown that one quarter of human breast tumours have EEF1A2 gene amplifications, meaning that they have more copies of EEF1A2 DNA than normal breast cells. EEF1A2 is capable of increasing the growth rate of mouse and rat cells cultured in the lab. This implies that EEF1A2 promotes breast tumorigenesis. The prediction is that having more copies of the EEF1A2 gene causes breast tumour development and is associated with poor clinical outcome. One of the goals of this proposal is to test this by measuring the number of EEF1A2 genes in breast tumour samples and determining whether patients whose tumours have more EEF1A2 genes do better or poorer that those with normal copies of eEF-1a2. To this end, researchers will design antisense oligonucleotides, a promising new anti-cancer agent, that inactivate EEF1A-2 and test their ability to halt the growth of tumors in a mouse model of breast cancer.