Anti-Indigenous discrimination and racism are pervasive in healthcare across BC. One contributing factor is the language that is used to describe First Nations, Inuit, and Métis (FNIM) peoples. Language is powerful, and the words we read, hear, and use can change the way we think and behave. Unfortunately, many of these words about FNIM peoples are negatively biased. With continued exposure to this negative language, particularly in the published health literature, healthcare providers can develop negative feelings and thoughts about FNIM peoples, which can lead to biased action, and ultimately culturally unsafe care. Our goal is to develop equity-centered language to reduce anti-Indigenous racism in healthcare. In collaboration from the outset with FNIM researchers, healthcare providers, patients, caregivers, and community members, we will use Indigenous research methods to co-develop tools that provide specific and concrete guidance to identify and prevent the use of negative, deficit-based language, while providing and promoting positive language, starting with cancer care. Adapting how we communicate in healthcare and research will bring us one step closer to culturally safe care for FNIM peoples in BC and nation-wide.
Research Location: BC Cancer - Vancouver
Toward an immunohistochemical model for molecular subtyping and predicting of treatment response in bladder cancer
Bladder cancer has an increasing incidence in North America and represents a significant healthcare burden. At the molecular level, it is a diverse disease with heterogeneous clinical outcomes and treatment responses. Immunohistochemistry (IHC) has been applied to predict molecular subtypes with good reliability. In our previous study, we calculated the accuracy of uroplakin II (UPII), a marker of urothelial differentiation, to predict molecular-based luminal versus basal subtypes of bladder cancer. Our previous proteomics studies have also identified a list of potential proteins associated with the patients’ prognosis and chemotherapy response. The overall objective of the current study is to identify an IHC marker panel to accurately predict the molecular subtypes of bladder cancer and their response to chemotherapy. This proposed study will demonstrate that IHC markers could reliably identify the luminal and basal molecular subtypes. The semi-quantitative visual assessment of these markers in routine pathological preparations will be a valuable tool in identifying bladder cancer’s molecular subtypes and improving the selection of MIBC patients most likely to benefit from neoadjuvant chemotherapy.
Investigating novel, non-chemotherapy, targeted treatment strategies in high grade serous ovarian cancer
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.
Clinical applications and implementation of artificial intelligence in lung cancer: predicting treatment response in advanced disease and risk of malignancy in lung cancer screening
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 detection using the lung microbiome and exhaled breath
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.
Objectives:
- 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.
Phrenic nerve pacing to improve outcome in mechanically ventilated patients with acute respiratory distress syndrome
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.
Molecular determinants of pathogenesis and clinical outcomes in high-grade B-cell lymphoma
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.
Self reactivity as a driver of extranodal diffuse large B-cell lymphoma transformation and survival
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.
Post-transcriptional regulation of hematopoietic stem cell function during normal and malignant hematopoiesis
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.
Exploring oxidative phosphorylation as therapeutic vulnerability in high risk acute myeloid leukemia
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.