Prostate cancer researchers at The Institute of Cancer Research, London, are launching two new collaborations that will make use of cutting-edge genetic technology to help improve patients’ treatment options, thanks to a $750,000 funding boost.
The Institute of Cancer Research (ICR) scientists will receive a share of two of nine $1 million Challenge Awards that the Prostate Cancer Foundation opened to researchers around the world in an effort to address the most challenging problems in prostate cancer research. The projects will be led by Professor Johann de Bono, leader of the prostate cancer targeted therapy team at the ICR and honorary consultant at The Royal Marsden NHS Foundation Trust, and Dr Gerhardt Attard, Cancer Research UK Clinician Scientist at the ICR.
Mutations may differ between cancer cells
The first project aims to reveal the true diversity in genetic mutations in prostate cancers, even within an individual patient’s body. Their study follows a landmark paper published last year by project leader Professor Charles Swanton from University College London, who found substantial genetic variation between different parts of individual patient’s kidney tumours, and in particular differences between tumours at the original site and once the disease had spread. The team will investigate to what extent the finding applies to prostate cancer, and how this affects the way prostate cancer patients should be treated.
The study may help explain why targeted cancer treatments chosen on the basis of a single tumour biopsy are not always effective, and also how cancers can develop resistance to treatments. It is important that clinicians understand a tumour’s true identity before deciding on the most appropriate method of treating it, so the study could also lead to a change in the way scientists collect samples and assess prostate cancers.
The team will carry out deep genome sequencing on multiple biopsies taken from 20 prostate cancer patients at different stages of disease, including localised cancer and cancer that has spread. As well as characterising the diversity of tumours within patients, they will also seek to determine the key genetic mutations that drive disease growth and spread, which could be targeted with new drugs.
The ICR team will receive half the £1 million funding allocated to this project.
Complete picture of key gene faults
In the second project, the team is seeking to build a complete picture of genetic pathways that are often faulty in prostate cancer and are therefore an important treatment target. The DNA damage response pathways are effectively a cell’s repair kit, helping correct damage to the genome that occurs during an organism’s lifetime.
The team will identify the range of faults present in these pathways in prostate cancers and determine how common each is at different stages of the disease, and what role it plays in driving the disease. This knowledge will bring doctors a step closer to fully personalised medicine, in which the genetic faults driving each patient’s cancer will be assessed so they can be given drugs that directly target these faults.
One particular focus for the team are faults in the gene PARP, which is often over-active in tumours of patients with advanced prostate cancer. PARP has a dual role – as well as helping repair damaged DNA, it also helps prostate cancer cells interact with the male hormone testosterone, which they rely on for growth. PARP-blocking drugs have been developed that attack tumour cells by both preventing them from repairing mistakes in their DNA, and also halting their growth by suppressing their use of testosterone.
This dual role raises the potential that it could be useful in treating patients with advanced cancer who have become resistant to hormone-blocking treatments. As part of the project, the team will evaluate whether combining a PARP inhibitor with a new-generation hormone treatment can overcome treatment resistance.Professor de Bono’s team will receive a quarter of the $1 million funding for this project, which is led by Dr Karen Knudsen from Thomas Jefferson University and supported by the funding from the 2011 Movember United States campaign.
Both two-year peer-reviewed grants are designed to support “highly innovative” research projects that have the potential to benefit patients in the near term.
Dr Howard Soule, executive vice president and chief science officer of the Prostate Cancer Foundation, said the “promising” research projects selected aimed to change clinical practice and improve outcomes for patients with advanced disease.