These significant funds will allow the investigators to build and conduct programs of cancer research for up to seven years.
Their research spans several important areas of cancer, including new targets of vulnerability for epithelial cancers, developing novel radioactive agents and examining how malignant cells evade the immune system in certain lymphoid cancers. Read more about each research project below.
The grants were received from the Canadian Institutes of Health Research (CIHR) as part of its Foundation Scheme – a federal health research funding initiative designed to foster a sustainable foundation of new and established health research leaders in Canada.
The Foundation Scheme’s ultimate objective is to provide long-term support for the pursuit of innovative and high-impact research programs conducted by investigators at any career stage and across CIHR’s mandate. More information is available from CIHR
Cancers evolve over time and the gene mutations driving them can change. A major bottleneck in the treatment of epithelial cancers is a lack of diverse therapeutic and treatment options. This is especially relevant in cancer, as tumours are able to evolve and adapt to "escape" from single-agent treatment. This is similar to what occurs in antibiotic-resistant bacteria, where a combination of drugs is required to treat an infection. Breast cancers, for example, often develop drug resistance so that their tumors recur. Mutational evolution likely underlies this event.
It is critical to identify new options and approaches to target tumours that have become drug-resistant as a result of mutational evolution. It is known that clonal complexity — the so called "cellular superbug" phenomenon — is associated with instability in the tumour's genetic sequence driven by the inability of DNA to repair itself. Dr. Aparicio’s team hypothesizes that there are specific sections of the genome with unique DNA structures may be targetable through directed approaches and they plan to explore novel approaches that target these structural vulnerabilities within the human genome.
By combining chemical genomics of DNA targeting with genetic technologies to uncover conditional genetic interactions and methods for measuring clonal structure, Dr. Aparicio’s team expects to derive a completely new mechanistic approach to targeting genomically unstable epithelial cancers. Their studies have the potential to answer specific questions about how breast cancer arises, progresses and becomes resistant to treatment. These findings will have a global impact within the cancer research community, allowing for the design of improved and more effective therapies. In short, the practical application of cancer cell genetics will become a reality in the clinic, representing a significant step forward in direct translational benefits for patients.
Dr. Bénard’s research team will develop novel imaging and therapeutic agents, which have radioactive tags ("radioisotopes") that bind to markers found specifically at the surface of cancer cells. This allows for them to be delivered to specific cancer sites while avoiding healthy tissues. These markers are then observed using a sensitive imaging method known as positron emission tomography (PET) that can be combined with other imaging methods such as computed tomography (CT) or magnetic resonance imaging (MRI) scans.
Dr. Bénard’s team has developed several compounds that home in on cancer cells with very high accumulation relative to healthy surrounding tissues. As part of this research, these scientists will continue to develop and improve new compounds to deliver a radioactive payload to cancer cells for diagnosis or treatment. They will focus on introducing these radiopharmaceuticals in early phase clinical trials to set the stage to evaluate them across centres in Canada.
Some radioisotopes can be used for treatment to deliver radiation that localizes to cancer from an intravenous injection. The research team will use potent radioisotopes, called alpha emitters, to kill cancer cells while minimizing damage to normal organs. Imaging probes that have exceptional signal in tumours, with minimal accumulation in normal tissue, are very promising for this purpose.
The anticipated outcomes of this research program will be the introduction of novel imaging agents in the clinic to benefit patients suffering from breast, prostate and other cancers. The radiotracers will be shared with facilities across Canada, with the goal of multi-centre clinical trials, and eventual introduction into clinical use. Canadians will benefit by gaining early access to new imaging technologies as well as proper cancer staging with the goal of improving survival and reducing mortality for cancer patients. Ultimately, with the appropriate radioisotope, some of these compounds will also be suitable to treat patients with advanced cancers that do not respond to conventional approaches.
Lymphoid cancers are the fifth most frequent cancer in humans, affect patients of all ages and, despite generally effective treatments, a significant number of lymphoid cancer patients still die of their disease. This is despite the fact that, in certain subgroups of lymphoid cancers, the malignant cells are surrounded by normal immune cells, yet these cells are unable to muster an effective immune attack against the tumor.
In recent years, researchers have made significant progress in understanding how the malignant cells are evading the immune system. However, this improved knowledge has not yet been successfully translated into better treatments for patients. Dr. Steidl’s research team will focus on two related subtypes of lymphoid cancer — called Hodgkin lymphoma and Primary mediastinal B-cell lymphoma — that often affect adolescents and young adults. They will study the exact mechanisms of immune system escape investigating certain genes that they have found altered in their earlier studies. Dr. Steidl’s team will focus on the effect of these alterations on tumor surrounding immune cells to characterize novel drug targets and to pave the way for innovative clinical trials. Moreover, they will focus on the development of genetic tests that predict therapy resistance in childhood and adult Hodgkin lymphoma and identify patients at high risk of relapse.
Dr. Steidl’s studies will be very important for physicians and patients as this research will result in the development of clinical tests that will provide information about the individual prognosis of lymphoma patient and will help developing new drugs and personalized treatments. Ultimately, these treatment improvements will lead to higher cure rates and fewer side effects for patients suffering from malignant lymphomas.