As the fifth most common cancer in B.C., bladder cancer has the third highest mutation rate of all cancers, and is often associated with low treatment response and poor survival rates for advanced-stage patients.
Today, Dr. Bernie Eigl and his team at BC Cancer are at the forefront of improving patient outcomes for this difficult-to-treat cancer through targeted therapies, clinical trials and innovative research. Work is currently underway to better understand the characteristics of bladder cancer, which has resulted in the identification of several unique subtypes and mutations that continue to shed light on why treatment often fails.
Because of donors like you, work continues to forge ahead that is bringing hope to families across B.C. and beyond.
Studying CTDNA to Develop Targeted Therapies
A collaborative study currently underway at BC Cancer and Vancouver Prostate Centre aims to determine whether circulating tumour (ctDNA) collected via a blood sample from patients with metastatic bladder cancer could help identify mutations that correspond to treatment response or resistance, so that the most effective, targeted treatments can be offered to patients as soon as possible.
Thanks to recent technological advancements, leading experts at BC Cancer are now certain that ‘circulating tumour DNA’ (ctDNA) has a powerful role to play in the future of cancer care: not only does ctDNA signal the presence of cancer in its earliest stages, it has the potential to reveal the unique mutational profile of each patient’s cancer and predict their response to treatment.
Over the past two years, BC Cancer researchers have established a suite of custom tools and bioinformatics pipelines designed to capture and analyze ctDNA in metastatic bladder cancer, but the potential clinical uses of ctDNA for bladder cancer remains largely unexplored.
Enter BC Cancer Biomarker Program
The overarching goal of this program is to learn about bladder cancer and discover bio-markers or “signatures” that might help experts determine which cancers respond to which treatments.
Under this program are three key projects that will culminate in clinical trials to determine if the biomarkers are truly effective in predicting patient response.
Philanthropic funding for the following three projects will leverage these grants, enabling larger-scale evaluation to determine the value of bringing these approaches to people in the clinic.
Project I: Investigating DNA Repair Defects in Metastatic Bladder Cancer
Platinum-based chemotherapy is the first-line treatment for metastatic bladder cancer. Fifty per cent of patients respond positively, but those who don’t are often not well enough to undergo further treatment. For this reason, validated clinical biomarkers to help predict response ahead of time are urgently needed.
The primary goal of this project is to evaluate whether mutations or deletions in DNA repair genes (detected in ctDNA) can predict a person’s sensitivity to platinum-based chemotherapy.
The impact of this project will be to establish a practical tool to identify people most likely to benefit from platinum-based chemotherapy, and prioritize those unlikely to benefit for alternative therapies and clinical trials.
Project II: Studying the Role of T-Cells in Bladder Cancer
Immune checkpoint inhibitors (ICIs) are drugs that block proteins. They enable a person’s T-cells to more effectively kill cancer cells.
The introduction of ICIs for bladder cancer has led to a major breakthrough in the treatment of this disease. However, clinical trials have seen response rates of only 15-20% and no reliable biomarkers have been established to predict who will respond. In order for a response to occur, the right kind of cancer-killing T-cells have to be present in the tumour.
The aim of this project is to investigate whether T-cells can be used as predictive biomarkers for bladder cancer.
In this feasibility study, T-cells will be isolated from patients’ blood and characterized to see if they correspond with response to ICIs and if ICI exposure leads to changes in T-cells.
Scientists at BC Cancer’s world-renowned Terry Fox Laboratory have developed and validated two tests to identify T-cells. This will be one of the first times that this technology will be used in the world of bladder cancer.
Results from this pilot project will enable scientists to validate these findings on a national scale.
Project III: How “Mutational Signatures” Impact Treatment Response
Immunotherapy-based treatments have significantly improved outcomes for people with advanced bladder cancer. A small proportion of patients have experienced a dramatic and lasting response. However, experts are currently not able to predict who will benefit from immunotherapy-based treatments in advance.
For immunotherapy to work, the immune system must recognize abnormal proteins generated by cancer cells as foreign and mount an attack.
The aim of the third project is to analyze the cancer DNA present in the blood to identify mutations specific to each person’s bladder cancer.