Bladder Cancer

The fifth most common cancer diagnosis in British Columbia, most bladder cancer patients initially respond well to chemotherapy, yet the five-year survival rate is only 5-15%.

LOW-TREATMENT RESPONSE, NEW HOPE

Currently, metastatic bladder cancer patients receive chemotherapy as a first line treatment, followed by  immune checkpoint inhibitors (drugs that block proteins to allow immune cells to more easily kill cancer cells), but less than 50% of patients respond to either treatment.

While an advanced bladder diagnosis is often deadly, because of research, there is new hope.

Knowledge of the genetic characteristics of bladder cancer is expanding and researchers have identified several unique subtypes. They have also discovered that bladder cancer has the third highest mutation rate of all cancers, which explains why treatment often fails. 

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.

This approach is promising for bladder cancer, given the high mutation rate and known release of abundant ctDNA into the blood.

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. 

You can support Bladder Cancer Research

For more information, contact

Alyson Killam
Senior Director, Development
PH: 604.877.6160
akillam@bccancer.bc.ca