About 3,000 Canadians receive a diagnosis of ovarian cancer (OC) each year. Despite initial good responses to treatment, the chance of long-term survival is low with ~30 percent of patients living five years from diagnosis. Drugs called PARP inhibitors improve survival but only in about half of patients. Small clinical trials have shown promising results using chemotherapy-free PARP inhibitor targeted drug combinations. This proposed research asks several important questions:
- Do chemotherapy-free targeted treatments work in OC and which drug combinations are best?
- Which order treatments should be given, before or after chemotherapy?
- What are the features of OCs that do not respond to PARP inhibitors and can we find new targets?
We will use samples from two groups of patients to conduct the research: from a clinical trial called NEOCATS and from OC patients that did not respond to PARP inhibitors given as standard of care in BC Cancer sites. NEOCATS trial will run across Canada and is led by BC scientists. Laboratory studies will take place in our Vancouver labs and will use novel mice models to study how OC responds to different treatment combinations. Patient partners with lived experience of OC will help guide the project.
Treating advanced disease and early detection are two main challenges in lung cancer. More than half (~55 percent) of people with advanced disease are unlikely to respond to a simple standard treatment. We’ll use advanced computer-assisted analysis technology to assess a special form of x-ray — computer tomography (CT) imaging to identify people less likely to respond to usual care. This, in turn, will allow care teams to provide more appropriate care decisions. Lung cancer screening uses CT to monitor abnormalities in the lungs. Some people with “normal looking” lungs on CT may rapidly develop aggressive cancer before the next CT appointment. We will use advanced technology to assess the “normal looking” lung CT images to identify early cancer-related changes in the lung tissue that can not be seen by the human eye. This research will guide personalized care decisions and improve the survival of people with lung cancer in BC. Our multidisciplinary research team at BC Cancer Vancouver includes cancer care clinicians, scientists, and patients and families with lived or living experiences with lung cancer. We will ensure the needs and priorities of those most likely to be impacted by our research will be integrated throughout the research.
Lung cancer is the leading cause of cancer death worldwide. The number and proportion of lung cancers in people who have never smoked is projected to outpace active smokers in the next 25 years. Evidence indicates that outdoor air pollution, specifically one of its major components, particulate matter (PM 2.5), consisting of small particles measuring less than 2.5 microns in the air, is a major cause of lung cancer in never smokers. Chronic exposure to PM 2.5 can affect the layer of bacteria lining the lung (lung microbiome), changes in the lung microbiome referred to as dysbiosis have been shown to occur 10 years prior to a lung cancer diagnosis, signaling an increased risk for cancer. A promising, non-invasive tool to detect dysbiosis in the lung microbiome is studying the components of exhaled breath.
- Define the lung microbiome composition and function in people who never smoked, with and without lung cancer, including the effect of high levels of air pollution by direct bronchoscopic sampling.
- Use exhaled breath to detect early lung cancer in people who have never smoked based on the differences in the lung microbiome between cancer and non-cancer individuals.
Our lungs normally work by the diaphragm contracting and pulling air into our lungs. The mechanical ventilator is an amazing invention that blows air into the lungs to inflate them. However, research has shown that this can cause lung, diaphragm, and brain injury. Recently, the intravenous catheter that is used in almost all ICU patients has been modified to have the ability to send a directed pulse of electricity across the blood vessel wall to activate the nerve that travels from the brain to the diaphragm, called the phrenic nerve. By sending a carefully directed electrical pulse, the diaphragm can be activated even in patients who are deeply sedated and critically ill. We have shown in a pig model that when this is used in conjunction with mechanical ventilation, it can protect the lung, diaphragm, and brain from injury. We propose studying patients who have low-oxygen levels and are acutely ill. Our team at Royal Columbian Hospital has extensive experience with this novel intervention and will be partnering with a multi-disciplinary team, including patient partners, to carry out this patient-oriented research. This work has the potential to improve patient outcomes and save the healthcare system valuable resources.
One-third of patients with aggressive non-Hodgkin lymphoma relapse after conventional chemotherapy and die of their disease. We need new methods to identify, at diagnosis, which patients have a high risk of relapse to improve their treatment. Genetic profiling is a powerful tool that can identify these high-risk patients. ‘Double-hit lymphoma’ (DHL) is one type of lymphoma that responds poorly to standard treatment. Current testing strategies cannot accurately identify all patients with DHL. We aim to improve the identification and treatment of DHL with a new test that uses a unique ‘genetic blueprint’. We will apply this test on lymphoma samples from 900 aggressive lymphoma patients in British Columbia to find out its ability to identify DHL patients compared to current methods. Patients who carry this genetic blueprint may benefit from different treatment approaches that overcome the high risk of relapse. We will also conduct an in-depth genetic analysis of DHL to understand how these lymphomas develop in the body. This new knowledge will help design smarter therapies that target the tumour while sparing normal body cells. These ‘targeted therapies’ can avoid the significant side effects caused by intensive chemotherapy.
Lymphoma is a form of cancer that affects immune cells called lymphocytes, a type of white blood cell. There are many subtypes of lymphocytes and lymphomas. Diffuse large B-cell lymphomas (DLBCL) develop from B lymphocytes (B-cells) and are the most common subtype of non-Hodgkin lymphoma. About one third of DLBCL extend beyond the lymph nodes (“extranodal DLBCL”), and invade vital organs such as the kidneys, lungs, and brain, with an often-fatal outcome. Our ability to predict which patients will develop extranodal DLBCL is limited, and we also lack disease-specific treatments, partly due to an incomplete understanding of how and when these tumors originate. Interestingly, recent evidence suggests extranodal DLBCL share features with autoimmune disorders — conditions in which lymphocytes abnormally react against organs in our bodies, instead of external foes. In this study, we will investigate the relationship between the origin and progression of these diseases, in an effort to better understand how B-cells transform into cancerous cells, disseminate, and expand. Our work could help identify patients at high risk of developing extranodal DLBCL, and unveil key tumor dependencies to be leveraged as specific therapeutic targets.
In 2016, there were approximately 22,510 Canadians living with leukemia and an estimated 2,900 Canadians died from leukemia. Acute myeloid leukemia (AML) is one of the most common types of leukemia in adults. About 30 percent of AML patients eventually relapse after treatment and suffer from very poor overall survival at this stage. It is postulated that leukemia stem cells (LSCs), a small population of leukemia cells characterized with regenerative ability, mediate resistance and relapse after therapy. My work sought to uncover the largely unknown role of the processes that control protein generation in maintaining blood stem cells and how it contributes to transformation of leukemia stem cells in cancer. This research program aims to identify new factors, which can serve as targetable molecules and pathways to specifically eliminate leukemia cells while sparing normal cells. The work will provide the scientific foundation for future developments of therapy targeting these pathways as a novel strategy in eradicating leukemia stem cells to improve outcomes in AML patients.
The standard of care for AML patients was introduced in the 1970s and has not significantly changed since then. Patients suffering from acute myeloid leukemia (AML) with unfavourable genetics are characterized by dismal overall survival due to poor treatment response to standard chemotherapy. In this research proposal, I aim to better understand the energy metabolism of high-risk AML cells and explore this as a novel treatment avenue. My research will create a rational for future clinical trials to improve patient care and develop novel treatment perspectives for a patient collective with a bleak prognosis.
T cells patrol the body using their T cell receptors (TCR) to look for cells which display evidence of intracellular pathogens or cancers. In order to focus their attention on specific cancer antigens, T cells can be engineered to express an artificial recognition receptor (termed a Chimeric Antigen Receptor or CAR). CAR technology has been shown to be extremely powerful clinically in leukaemia and lymphoma patients who have not responded to other lines of therapy, leading to recent FDA and Health Canada approvals.
However, only one third of lymphoma patients treated with CD19 specific CAR T cells exhibit long lasting curative responses, thus leaving significant room for improvement. CAR T failure can usually be attributed to either loss of the tumour antigen (ie CD19) or to dysfunction of the T cells, and we are developing a strategy to address the latter. Once T cells express a CAR, they can still receive signals through their TCR, and we have shown in preliminary experiments that this type of stimulation can help CAR T cells to proliferate and kill tumour cells. Our research will use oncolytic cancer killing viruses, and other vaccines, to help mobilize CAR T cells which recognize viral antigens using their TCR.
- Jessica Nelson
Canada’s Michael Smith Genome Sciences Centre
- Lindsay Zibrik
BC Cancer – Vancouver
- Kirstin Brown
Canada’s Michael Smith Genome Sciences Centre
- Kevin Sauve
Canada’s Michael Smith Genome Sciences Centre
The Personalized Oncogenomics (POG) program at BCC is a patient-driven clinical research project which uses genome sequencing to inform cancer treatment and care. Delivery of the POG program involves a diverse group of stakeholders, all with varying health literacy levels. To close the literacy gap, POG must explore new knowledge translation channels to improve health literacy and education.
Knowledge translation is becoming increasingly common in clinical practice. Best practices recommend the use of lay language and to present material in popular, engaging and creative formats such as video and online content to reach and engage a large audience. Research suggests one of the most effective methods is through animated videos (Meppelink et al., 2015; George et al., 2013).
The goal for this project is to develop a short, patient- and public-focused animated video about the POG program and to showcase the video to our knowledge users in a web-based format. Outcomes include improved awareness about the POG program, improved health literacy for patients considering POG or healthcare professionals new to POG, and improved understanding of how POG supports and enhances patient care in BC.
Award Update: March 2022
The POG Knowledge Translation working group produced an animated video that explains cancer, genomics, and precision medicine using vocabulary and engaging graphics (in six languages) suitable for many audiences, from experts to those with no knowledge of the science.
Learn more on Genome Sciences Centre’s website.