Millions of Canadians and their families are affected by cancer—an illness that is not a single disease, but an enigmatic one comprised of over 100 subtypes. The complexity of cancer and its impact on so many people has researchers worldwide hunting for clues. Today more than ever before, increasingly sophisticated technologies and an escalating pace of discovery are leading to improved diagnoses and treatments.
Researchers at the Samuel Lunenfeld Research Institute of Mount Sinai Hospital are working to understand the genetic and molecular events that underlie many types of cancer, as well as identifying targets for early detection, understanding metastasis, and developing new therapies. A better understanding of these mechanisms will help enable personalized medicine, so that physicians can optimize treatments based on an individual’s specific form of cancer.
Pinpointing environmental triggers
Can our experience and environment impact gene expression and our fundamental biochemistry? How our environment impacts our risk of illness is a key focus of researchers in the Prosserman Centre for Health Research at the Lunenfeld.
Principal Investigator Dr. Julia Knight studies breast cancer prevention in populations, with a focus on the environmental and genetic factors that confer an increased risk of the illness. For example, her team has found strong evidence suggesting that vitamin D could help prevent breast cancer.
In collaboration with other Lunenfeld investigators, Dr. Knight is leading a new project that will help scientists study complex diseases including cancer, through the use of innovative statistical methods to analyze large data sets. Dr. Knight is also conducting studies to assess the impact of age of menarche (i.e., the onset of first menstruation), oral contraceptive use, and other factors, on breast tissue development and the risk of breast cancer.
Working with Dr. Knight in the Prosserman group, Dr. Lyle Palmer is a Lunenfeld Senior Investigator and Executive Director of the Ontario Health Study—the largest volunteer cohort study ever conducted in Ontario, aimed at investigating the factors that increase individual and community risk of developing cancer and other common illnesses. The study will pay special attention to the complex interplay of factors that underlie the development of many of the most common and/or chronic diseases.
“This study is a game changer,” says Dr. Palmer. “We hope the results will change how we practice clinical medicine, how we conduct research, and how we turn research into clinical practice.”
“To really understand health and diseases such as cancer, we need to learn more about variation from person to person, the underlying causes, and also what changes over time and why,” says Dr. Knight.
Defining the role of ‘epigenetics’
Just how the environment‘imprints’ on our genetic blueprint is the focus of epigenetics—the study of changes in gene activity that do not involve alterations to the genetic code, but still get passed down to at least one successive generation.
These patterns of gene expression are governed by the cellular material surrounding our DNA. It is these epigenetic ‘marks’ that determine whether genes can be switched on or off, and thus determine their functions. It is through epigenetic marks that environmental factors like diet, stress and prenatal nutrition can make changes to genes that are passed from one generation to the next.
The field of epigenetics examines changes in gene function that do not disrupt the underlying DNA sequence, but are instead reversible changes that shape the responsiveness of genes. Genetics, on the other hand, studies permanent or heritable changes in genetic function.
At the Lunenfeld,scientist Dr. Bharati Bapat is looking at colorectal, prostate and bladder cancer through the lens of epigenetics. For example, DNA methylation (the addition of a specific chemical compound, or a chain of them, to a cell’s genetic material) is a naturally occurring process that can cause a potentially reversible change in a gene.
“Frequent, abnormal increases or decreases in DNA methylation are found in most human cancers and contribute to their development,” says Dr. Bapat. “Each tumour carries its own unique pattern, or signature, of DNA methylation. By studying changes in DNA methylation, we aim to take this additional information into account in predicting the behaviour and responsiveness of cancers to specific treatments.”
Hunting for substances or ‘markers’ to detect cancer
Associate Scientist Dr. Eleftherios Diamandis and his team at the Lunenfeld are discovering and evaluating new biomarkers (a term referring to a protein measured in blood whose concentration reflects the severity or presence of some disease state) for the diagnosis, prognosis and monitoring of cancer and other illnesses. The development of new biomarkers is important because when cancer is diagnosed early, it is more likely to be treatable. Dr. Diamandis and his team are working to identify simple diagnostic tests for the early detection of cancer, specifically cancer of the prostate.
“There are significant data confirming that early diagnosis is the cornerstone of winning the fight against cancer,” says Dr. Diamandis.
Prostate cancer is the most frequently diagnosed cancer in men, and the second leading cause of cancer mortality. More than 50 per cent of men over the age of 80 develop some form of latent or aggressive prostate cancer. Currently, there are no effective methods for preventing this cancer; the best way to combat the disease is by early diagnosis (with prostate-specific antigen test, or PSA) and administration of optimal therapy.
Dr. Diamandis and his team are working to more accurately diagnose prostate cancer through the development of more specific, non-invasive procedures such as simple blood tests that measure the levels of specific biomarkers. These tests will avoid a considerable number of prostatic biopsies in patients who have a positive PSA but are later found to be cancer-free.
Targeting sub-types of cancerous tumours
New cancer treatments targeted to specific tumour sub-types are on the horizon, and clinician-scientists in Mount Sinai’s Sarcoma Program are breaking new ground in this area. A team led by Dr. Rebecca Gladdy, a scientist and surgical oncologist specializing in soft-tissue sarcomas (cancer of the connective tissue), has developed a new way to test upwards of 30 genes concurrently, allowing for a more efficient and accurate model of cancer, compared with standard methods in which only one of a handful of genes are measured. Her team has developed cell lines that can be used to assess molecular changes in tumours to better predict patient outcomes, and help in the development of more sophisticated, targeted drugs.
“We can validate which genes are important and those that can help develop newer, less toxic and more targeted treatments,” says Dr. Gladdy.
For example, her team is using these methods to assess the effects of doxorubicin—a cancer drug sometime associated with toxic effects including heart disease—to find a complementary or alternate drug candidate that can be used to develop newer, more durable and tolerable treatments.