Vancouver prostate cancer team takes aim at “nasty” tumours that become drug resistant
Significant progress has been made in treating prostate cancer, but survival rates remain low for the most advanced, drug-resistant forms of the disease – a reality the TFRI’s prostate cancer progression team based in Vancouver, BC is working to alter.
“We’re looking at the tumours that are the nasty ones. They come back after treatments, progress to castrate resistance, and will eventually kill the patient if there’s no intervention,” says Dr. Paul Rennie. He and Dr. Martin Gleave co-lead the multi-disciplinary 20-person Terry Fox New Frontiers Program Project Grant group at the Vancouver Prostate Centre (VPC).
The major problem with advanced forms of prostate cancer is that existing drugs work only for a limited period of time before the cancer cells become resistant, Dr. Rennie explains. Prostate cancer is the third leading cause of cancer-related death in Canadian men, and one of the most common cancers for this demographic.
“Some men will survive for years with the current treatment protocol, and their disease will be held in check. Others will progress quickly to a form where they no longer respond to these drugs,” says Dr. Rennie. “Our goal is to prolong life and possibly, through multi-targeting of different key elements within the tumour, effect a cure.”
The PPG team’s six sub-projects are focused on several key areas:
- The target discovery project uses next-generation sequencing techniques to see if a “genetic footprint” is left behind for men who become resistant to drugs;
- The cell biology mechanisms team is determining if destroying the protein clusterin, which is created to protect cancer cells, will result in “a bigger bang with the actual therapeutic treatment”; and
- Two other team projects are investigating molecular and cell targets, specifically two proteins (BIRC6 and Semaphorin 3C) that appear to be directly involved in preventing cancer cell death, to see if they contribute to treatment resistance.
The team has also discovered and developed the anti-clusterin drug OGX-011, which is being tested in a Phase III clinical trial, says Dr. Gleave, noting it shows a seven-month survival gain in a randomized Phase II study. Several other drugs are also currently in clinical trials, and therapies that inhibit Hsp27 and ERG, which encode proteins typically mutated in cancer, are also in the works.
“I hope the whole area of personalized medicine will reveal new ways to treat patients with old drugs. By looking at the genetic sequence of the tumour, we can tell you whether it’s going to be resistant to a specific drug, or sensitive to it,” says Dr. Rennie. “It’s a very exciting time...I’m very hopeful about the future.”
Project Title: The Terry Fox New Frontiers Program Project Grant in Prostate Cancer Progression (2011-2016).
Investigators: Martin Gleave, Colin Collins, Emma Guns, Michael Cox, Chris Ong, Paul Rennie, Amina Zoubeidi, Yuzhuo Wang, VPC, UBC; Kim Chi, Shoukat Dedhar, Poul Sorensen, BC Cancer Agency.