Discoveries and Innovations
CANCER RESEARCH FOR THE GOOD OF THE PATIENT
Lung cancer is the deadliest one in industrialized countries. Not only is it responsible for more deaths in Canada than breast, colon and prostate cancers combined, but it is frequently diagnosed at a late stage in the course of the illness, which makes the curative therapeutic approach often impossible. During the last decade, significant progress has been achieved in the management and the molecular diagnosis of patients suffering from lung cancer, particularly the targeted therapies, the advances in immunotherapy as well as the liquid biopsies.
The medical practices in this sector are therefore constantly evolving and require the participation of several stakeholders in order to develop and to evaluate new technologies as well as to ensure the scale-up of better care for patients.
The thoracic oncology research team at the Institute is at the forefront of these medical advances. This team consists of respirologists, thoracic surgeons, oncologists and pathologists as well as researchers, including Drs. Philippe Joubert and Yohan Bossé. These two enjoy a unique academic and clinical setting in order to conduct their translational research program aimed at improving the investigation and the treatment of patients with lung cancer.
The work of Drs. Joubert and Bossé exploits cutting-edge genomics tools as well as biological material (DNA and pulmonary tissue) of patients operated on for lung cancer. Over the years, the Institute has established a biobank containing the most important world’s collection of lung tumours and non-tumour tissue. With the help of this resource, Drs. Joubert and Bossé seek to understand the genetic basis of lung cancer and can contribute uniquely to the sector international studies. This year, they have reported the findings taken from the most significant study examining the genetics of lung cancer. This research has allowed us to identify new predisposing genetic factors and genes involved in the development of lung cancer. The ultimate goal would be to develop genetic tests that will help identify individuals at higher risk and thus being able to facilitate the early detection. In addition, the novel genes unveiled by these works could lead to new treatment options. These also include that Drs. Bossé and Joubert are working at the present moment with the National Cancer Institute (NCI) in order to characterize the genetic basis of lung cancer, specifically in non-smokers.
Other projects have more immediate clinical designs. Drs. Bossé and Joubert have recently identified biomarkers to prevent recidivism after the surgery. The clinical implementation will allow us to better personalize postoperative treatments. The oncology research group is also at the avant-garde of emerging technologies. These include liquid biopsies and artificial intelligence. The group co-led at the present moment an important Canadian study for evaluating the performance and the effectiveness of the blood sampling in a patient diagnosed with lung cancer in order to detect one resistance mutation that is making people eligible for a targeted treatment. The implementation of this technique in the clinic will allow us to provide this molecular screening to a larger number of patients while minimizing the side effects and the costs to the health system. With regard to the artificial intelligence, the Institute has recently partnered with the company Imagia to study the radiological features of lung tumours in order to predict their clinical behaviour and their level of aggression. The artificial intelligence potential applications in respirology and in thoracic oncology are numerous and the Institute plans on getting actively involved over the next few years in this emerging field.
Through these activities, the Institute has established itself as a research engine in thoracic oncology. From fundamental discoveries to clinical applications, our researchers are transforming the lung cancer investigation and are ensuring the development of long-awaited treatments to fight this type that remains the deadliest. Working with health care teams, the Institute’s patients benefit from the best treatments available. A perfect model in translational research, the Institute has become a hub to evaluate novel therapies as well as emerging technologies of investigation, more importantly a must in thoracic oncology superspecialized care.
Philippe Joubert, M.D., Ph. D., FRCPC
Yohan Bossé, Ph. D.
CONSIDERING THE GUT MICROBIOTA TO PREVENT THE OBESITY-RELATED METABOLIC DYSFUNCTIONS
Obesity, particularly when accompanied by excessive visceral fat accumulation, and the ensuing systemic inflammation and metabolic disorders, such as type 2 diabetes, dyslipidemia, and ectopic deposition of triglycerides, are now considered a true world epidemic and a major cause of cardiovascular events as well as some cancer types. Furthermore, links between obesity or metabolic syndrome and neuroinflammatory and affective disorders are emerging. Among many others, two players have emerged which dysregulation appears to be both a predictive biomarker and causative factor of obesity: the endocannabinoid system – and signalling at cannabinoid CB1 receptors in particular – and the gut microbiome. It is now increasingly accepted that lifestyle conditions associated with obesity, such as a sedentary life and an excessive leaning towards a western-type diet, may disrupt the signalling at cannabinoid and other receptors involved in the control of metabolism by endocannabinoids and biochemically related mediators, on the one hand, and the healthy equilibrium of the gut microbiota, on the other hand, thus eventually leading to, or at least exacerbating, dysmetabolism and “dysbiosis”, respectively.
Intriguingly, recent discoveries point to the possibility that the dysregulation of endocannabinoidome, i.e. the complex signalling system comprising endocannabinoids, endocannabinoid-like mediators and their several receptors, may contribute to dysbiosis, and that the negative effects of the latter condition on insulin signal transduction, energy expenditure and fat accumulation may be partly mediated by disrupting the endocannabinoidome pathway. This vicious circle seems to feed also on commensal microbe-host cell interactions that favour the formation of endocannabinoids acting at CB1 receptors, while preventing the production of endocannabinoid-like mediators (some of which are even produced by, or with the help of, “beneficial” gut microbiota) at structures that, unlike CB1, instead counteract insulin resistance and excessive energy storage.
Several lifestyle interventions have been shown to combat both excessive signalling at CB1 receptors and obesity-associated dysbiosis in humans. For example, a one-year lifestyle modification program including healthy eating and physical activity was shown to reduce plasma endocannabinoid levels in correlation with reduction in visceral fat accumulation and circulating triglycerides, and similar interventions are also known to restore gut microbiota diversity and the prevalence of microbial species associated with lean and insulin sensitive phenotypes. The dietary intake of omega-3 polyunsaturated fatty acids has also proven to reduce endocannabinoid levels in association with the reduction of triglyceridemia, and ameliorate dysbiosis in obese men. Therefore, there is a very high potential for preventative lifestyle and nutritional approaches to reduce the negative impact of disrupted endocannabinoidome and gut microbiome signalling on obesity and type 2 diabetes. Furthermore, since dysbiosis and endocannabinoidome disruption are also associated with, and causative of, affective disorders in experimental models, it is possible that such preventative strategies will not only ameliorate obesity but likewise some of its associated CNS co-morbidities, such as depression and neuroinflammatory diseases.
The Canada Research Excellence Chair in the Microbiome-Endocannabinoidome Axis in Metabolic Health, started in June 2017, aims at fully investigating the biomolecular aspects of those commensal microbe-host cell interactions leading or contributing to obesity and related co-morbidities and cardiovascular diseases, and to subsequently develop new interventional (pharmacological, nutraceutical and nutritional) strategies for the prevention and treatment of these worldwide spread chronic societal disorders.
Vincenzo Di Marzo, Ph. D.
RESEARCH AND INNOVATION IN CARDIOVASCULAR IMAGING
Cardiovascular disorders, heart disease, and cerebrovascular accidents (CVA) happen to be the number one cause of sickness and death in Canada for both men and women (one loss of life every seven minutes). Behind these diseases lies atherosclerosis, a thickening of the vessel walls by the build-up of fat slowing down/blocking the passage of blood. It begins very early, silently, long before usual risk factors are emerging (elevated blood pressure, cholesterol at high levels, etc.) on which we draw upon to predict the hazard to health, making it difficult identifying patients in whom atherosclerosis is occurring in silence. This progression finally shows up, however, usually around 50 years or more, causing heart attack or CVA, hence the importance to identify patients at risk of such events.
The research work of Dr. Eric Larose focuses on the atherosclerosis in diverse populations with varying hazard levels in order to identify the disease characteristics that improve the prediction events by better understanding patients at risk.
Dr. Larose holds the Chair of Research and Innovation in Cardiovascular Imaging launched at Université Laval. This Chair’s mission is to identify and characterize the risk related to atherosclerosis through the development of the magnetic resonance imaging and the cardiovascular computed tomography, more specifically by creating and enhancing innovative methods of imagery by which clinical decision are to be made in secondary, primary and vital prevention regarding the conditions that involve narrowed or blocked blood vessels.
The interests of Dr. Larose include the context of how exercise contributes to the burden and the progression of atherosclerosis within the disease risk spectrum. He leads the MoMA study, funded by the Canadian Institutes of Health Research. It studies the links between atherosclerosis burden, lack of exercise, and visceral adiposity by exploring if the progression can be mitigated by a lifestyle modification with a focus on a moderate physical activity, whether it be in vital, primary or secondary prevention.
Dr. Larose, and his advanced cardiovascular imaging lab, which receives financial support from the IUCPQ Foundation, are involved in the cohort study of the Canadian Alliance for Healthy Hearts and Minds (Alliance canadienne pour des cœurs et des esprits en santé), a unique Canadian prospective one of nearly 10,000 participants. In addition to his contribution as a co-investigator, he is a member of the working group on imaging and the Alliance’s Cardiovascular MRI Core Lab head. Through his clinical and research activities, Dr. Larose contributes to advancing knowledge in order to improve the cardiovascular health of the general population.
Eric Larose, DVM, MD, FRCPC, FAHA