New Innovation Grants Announced by Canadian Cancer Society Research Institute

Although I am no longer employed by the Canadian Cancer Society (CCS) or the Canadian Cancer Society Research Institute (CCSRI), I retain not only a “soft spot” in my heart for both, but also a huge respect for the organizations and all they do, with always insufficient funds, to promote and fund excellence in cancer research in Canada.

One of the programs that was introduced while I was still there as VP Research was the Innovation Grant Program.

These grants represent the cream of the crop of some new cancer research ideas being brought forward. The whole Innovation Grant program was predicated on the idea that, when funds get tight (as they inevitably are) peer review processes get more conservative and risk averse. Creativity and innovation, always a hallmark of Canadian cancer research, sometimes gets de-prioritized in favour of less risky ventures. These grants are aimed at reversing that – the competition intrinsically is about accepting higher amounts of risk if justified by higher potential rewards. In other words, there is a higher than usual likelihood that many of these projects will not lead to bigger and better things, i.e., will “fail”, but the potential impacts of these make the risk worthwhile. Think of this as “venture capital”…

I am therefore pleased to see that the second round of new Innovation Grants has been announced and awarded.

The main announcement, and a in-depth description of one of the exciting new projects can be found on the CCS website.

Although summaries of all of these are  also listed on the CCSRI website, I have taken the liberty of reproducing the list of summaries of the new projects just awarded after adjudication by the Institute’s famed peer review process (he says humbly…).

Biomarkers and Genomics

Bapat, Bharati
Mount Sinai Hospital

Genome-wide distribution and dynamic regulation of 5-hydroxymethylation in prostate carcinogenesis
Dr Bapat’s group is undertaking a study using state-of-the-art technology that can be used to recognize a novel DNA modification to identify genes that are specifically malfunctioning in prostate tumours. The goal is to use these newly identified genes as prognostic markers and as a basis for more targeted therapies.

Dostie, Josee
McGill University

Discovering three-dimensional cancer epigenetics
Leukemia in children can arise when genetic material is naturally swapped from one chromosome to the next, creating a gene “fusion”. Dr Dostie is the first to study how gene fusions of the MLL (mixed lineage leukemia) gene are affected by the structure of the chromosome, and how these effects influence prognosis and survival of children with leukemia.

Durocher, Francine
CHUL – Centre hospitalier de l’Universite Laval

Characterization of an alternative spliced form of the DNMT3B methylation gene in breast cancer tumorigenesis
Specific genes have been shown to be strong predictors of breast cancer susceptibility; however these genes make up only ~25% of the familial risk, leaving 75% unexplained. Dr Durocher has identified a new susceptibility gene, DNMT3B, and is conducting a large-scale study looking at how this gene alters the genetic landscape of breast cancer cells.

Sladek, Robert
The Research Institute of the McGill University Health Centre (RI-MUHC)

Proteomics strategy to identify gene networks in cancer cachexia
Cancer cachexia, an often understudied complication of cancer, is a severe form of weight loss that drastically reduces the quality of life of cancer patients and accounts for over 30% of cancer deaths. To better understand the physiological mechanisms of cachexia, Dr Sladek is using a novel DNA-based technology to identify and isolate proteins involved in this complication, in hopes of improving outcomes for patients.

Gene Regulation

Busque, Lambert
Hopital Maisonneuve-Rosemont

Evaluation of the clinical and biological impact of TET2 mutation occurring in normal aging individuals, and identification of novel genes giving rise to a similar phenotype
The risk of developing myeloid cancer (a type of blood cancer) increases with age; however there are currently no tests available to identify individuals at risk. Dr Busque is conducting a study using blood samples collected from ~3000 aging individuals to find biomarkers that could be used to screen and potentially prevent cancer in those at risk.

Khokha, Rama
Ontario Cancer Institute/PMH

Identifying cell-of-origin and driver genes in breast cancer: a hybrid mutagenes approach
Dr Khokha’s laboratory has developed a new DNA-based technology called “insertional mutagenesis“ that can alter the genes of normal cells, “transforming” them into cancerous ones. Using this approach, Dr Khokha’s group is interested in determining which genes are responsible for different types of breast cancer, with the goal of developing new targeted treatment options and enhancing quality of life for patients.

Laird, Dale
University of Western Ontario

The novel channel-forming protein Pannexin 1 as a viable target for melanoma treatment
Dr Laird will be the first to assess the role of the Pannexin 1 protein, which is found in high levels on the surface of melanoma cells and is thought to be important in driving metastasis. He will determine whether this protein may be a suitable drug target for patients living with malignant melanoma which is responsible for 79% of skin cancer-related deaths and is often diagnosed at later stages, making it more difficult to manage and treat.

Malkin, David
Hospital for Sick Children

Biological and clinical impact of chromothripsis and early TP53 mutations on carcinogenesis in Li-Fraumeni syndrome
Chromothripsis- chromo for chromosome and “thripsis” meaning shattering into pieces – is a newly discovered phenomenon that causes massive chromosome destruction, similarly to a beaded necklace shattering into pieces and being reassembled haphazardly. Dr Malkin is studying how mutations in the genome-protecting gene known as TP53 can result in chromothripsis, causing a normal cell to become cancerous; thus improving our ability to monitor and screen individuals at risk because they are born with an abnormal TP53 gene.

Pelletier, Jerry
McGill University

DHX9 – Evaluating a novel anti-neoplastic drug target in vivo
One of the biggest challenges in cancer drug development has been to find drugs that target cancer cells and not healthy cells. Dr Pelletier is using mice to study a new target gene called DHX9, which if disrupted is thought to specifically cause cancer cell death and has great potential as a target for anti-cancer drugs in patients.

Sorensen, Poul
BC Cancer Agency (Vancouver)

The eEF2K translation elongation factor and tumour cell adaptation to metabolic stress
Cancer cells can easily adapt to new environments and recent evidence has shown that they are able to adapt to low levels of available nutrients by triggering survival pathways in the cell. Dr Sorenson is studying these “adapted” cancerous cells to determine whether eEF2K, which has previously been associated with poor outcomes in various cancers, is a suitable target for novel drug development.

Imaging and Technology Development

Chartrand, Pascal
University of Montreal

Studying telomerase activity and regulation in single cancer cells
Telomerase is an enzyme that is dysfunctional in various cancer types and drugs that act on telomerase are currently under clinical trial for different cancers. Dr Chartrand is working on developing a new assay that would make it possible to visualize telomerase at the molecular level, helping understand its role in the cell and the role of drugs acting on this important cancer target.

Czarnota, Gregory
Sunnybrook Research Institute

Photoacoustic monitoring of novel ultrasound microbubble-potentiated ceramide enhancement of hyperthermia
While heating (hyperthermia) has been used as an add-on to standard radiation therapy, it has yet to be used as a stand-alone option for treatment. Dr Czarnota is studying the effects of using hyperthermia along with microscopic bubbles and ultrasound — both which should enhance the heating effects on the tumour — as a treatment option that would be less invasive and more effective for cancer patients.

Foster, Paula
University of Western Ontario

Imaging the premetastatic niche
Cancers have the ability to spread and this spreading, known as metastasis, has few treatment options and drastically increases the mortality risk for patients. Dr Foster is using a powerful imaging approach, developed in her lab, that looks at how cancer cells change their environment to benefit themselves as they spread, in hopes of better understanding the way treatments should be administered to patients suffering from a cancer that has metastasized.

Jirik, Frank
University of Calgary

Developing an inducible transgenic system to study microRNA-mediated tumour vessel normalization
Conventional science says that cutting off the blood supply of a tumour would help in killing the cancer and prevent further growth and metastasis, however recent evidence has shown that this also has a negative impact on being able to feed the tumour with cancer-killing drugs. In a new approach to improving drug access to tumours, Dr Jirik is studying microRNAs — small molecules that help regulate the expression of genes in the cell — and how these can be harnessed to increase blood flow to tumours and in effect improve the ability to administer treatments to patients.

Lu, Qing-Bin
University of Waterloo

Development of novel photodynamic therapy via combination approach
Photodynamic therapy (PDT) is a new technology that uses light and light-sensitive materials to treat tumours without the harsh side effects of conventional cancer therapies. Dr Lu’s group is looking at improving PDT to make it easier to use on tumours that are difficult to treat because they are hard to reach or resistant to standard drugs, with the goal of making this therapy option more widespread throughout the medical community.

Zeng, Haishan
BC Cancer Research Centre

Raman spectroscopy based breath analysis for lung cancer detection
Early detection and treatment of lung cancer increases the 5-year survival rate of the disease to >90%. Drs Zeng and Lam are developing a new biochemical-based breath test for screening lung cancer that will make detection easier and more accessible to health care providers and patients.

Immunology, Signalling and Stem Cells

Marshall, Jean
Dalhousie University

The impact of combined histamine receptor (H1 and H2) blockade and local histamine release on tumour metastasis
While drugs that block histamine and its ability to trigger the immune response are widely used for helping minimize the side effects of cancer treatments, the body’s natural immune response is also thought to be an important player in the fight against cancer. Dr Marshall’s study will take an unconventional approach and look at how histamine can play a positive role in regulating the body’s ability to fight tumours, drastically impacting the way doctors manage all types of cancers.

Muthuswamy, Senthil
Ontario Cancer Institute/PMH

A novel 3D cell culture model for pancreatic cancer initiation and progression

Dr Muthuswamy has developed a new 3D model to analyze how pancreatic cells develop and grow. Dr Muthuswamy is now using this model to identify the molecular events that cause pancreatic cancer to develop from benign lesions, with the goal of finding better ways to control and treat one of the deadliest types of cancer.

Watts, Tania
University of Toronto

Control of B lymphoma through regulation of TRAF protein degradation
Proteins are often mis-regulated in cancer cells creating an imbalance that keeps the cells actively dividing and the cancer constantly growing. Dr Watts is studying TRAF1 — a protein that is hypothesized to be important in keeping lymphoma cells alive — and how using novel approaches like nutrient stress or RNA interference may reduce levels of this protein and help trigger death in the cancerous cells.

Novel Therapeutics

Diallo, Jean-Simon
Ottawa Hospital Research Institute

Combining chemical, genetic and in silico approaches to improve oncolytic virotherapy
Cancer-fighting viruses have been used to kill cancer cells in patients, however their effectiveness varies by tumour type. Dr Diallo is using mathematical and experimental models to combine these viruses with drugs that help promote their potency in cancer cells, creating a more powerful treatment option for patients.

Gunning, Patrick
University of Toronto

Structural optimization and mechanistic characterization of a novel and selective class of ubiquitin activatingenzyme-selective inhibitor
Drug resistance is a common problem in cancer treatment and therefore there is ongoing research to find new ways to target cancer cells. Dr Gunning proposes to use novel, highly-specific inhibitors developed in his own lab to target protein recycling in cells, thus cutting off the ability of the drug-resistant cells to grow and divide and providing a new way to treat cancer.

Korneluk, Robert
Children’s Hospital of Eastern Ontario

Synergistic combination of IAP antagonists and oncolytic viruses to treat cancer
Experimental drugs known as SMCs can trigger death in cancer cells without causing the toxic side effects seen with radiation or chemotherapy. Dr Korneluk is combining SMC drugs with other cancer fighting agents, including viruses, to increase their impact with the goal of starting a clinical trial to study these effects in humans.

McCart, J. Andrea
The Toronto Hospital (General Division)

Designing a next generation oncolytic vaccinia virus using high throughput functional screening
Vaccinia viruses are a type of virus that can be used to kill cancer cells. Drs McCart and Stojdl are performing a large-scale screen to find genes that improve the cancer-killing capability of these viruses, while also improving their overall safety to re-engineer a more potent and effective virus that could be used in patients.

Meyer, Francois
CHUQ – Laval University Medical Research Centre

Randomized controlled trial to test the efficacy of trans-tympanic injections of a sodium thiosulfate gel to prevent cisplatin-induced ototoxicity in patients with head and neck cancer
Cisplatin is a drug used for treatment of both childhood and adult cancers; however one of the common side effects of the drug is a loss of hearing. Dr Meyer is the first to conduct a clinical trial in 30 individuals using a safe and natural antioxidant known as sodium thiosulfate to study its ability in preventing hearing loss in patients being treated with cisplatin.

Tiedemann, Rodger
Ontario Cancer Institute/PMH

Better therapeutic targets to overcome drug-resistance and relapse in multiple myeloma
On average, patients with multiple myeloma only survive for five years after diagnosis and many patients develop resistance to conventional drugs. Dr Tiedemann is looking at the entire genetic code of drug-resistant cells from myeloma patients, to identify vulnerabilities in these cells that could be exploited for better detection and treatment options.

Prevention and Cancer Outcomes

Campbell, Tavis
University of Calgary

A randomized controlled trial of light therapy on biomarkers, sleep/wake activity and quality of life in individuals with post-treatment cancer-related fatigue
Cancer-related fatigue (CRF) is seen in 90% of cancer patients and is a serious symptom brought on by chemotherapy and radiation that can have a huge impact on the quality of life of patients, with 35% of patients experiencing persistent CRF even after the 5 year post-cancer benchmark. Light therapy has been used for fatigue associated with other diseases and this study led by Dr Campbell will be the first to assess the ability of light therapy to improve CRF in post-treatment cancer survivors.

Mabbott, Donald
Hospital for Sick Children

Exercise intervention in children treated with radiation for brain tumours
Radiation treatment for brain tumours kills healthy brain cells as well as cancerous cells, often impacting thinking capabilities in survivors. Dr Mabbott is studying the impact of exercise on children treated with radiation, and is looking for evidence that increasing physical activity in brain tumor survivors can stimulate the growth of new brain cells.

Virani, Sean
University of British Columbia

A prospective randomized placebo-controlled study of the effect of eplerenone on left ventricular diastolic function in women receiving anthracycline therapy for breast cancer
Anthracyclines are chemotherapy drugs used in the treatment of a variety of cancers, including breast cancer, which can have severe side effects, including heart failure. Dr Virani will study how a common medication that can prevent or reverse heart damage, known as eplerenone, can be used in concert with anthracyclines to improve clinical outcomes and quality of life for patients.

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