PG12-14 Cooper Lay summary
Principal Investigator: Professor Colin Cooper, Chair in Cancer Genetics at
the University of East Anglia
Lay title:
Creating new targeted combination therapies for patients with prostate cancer that has spread outside the
prostate (metastatic)
What are you proposing?
We aim to make a new therapy for treatment of advanced/metastatic prostate cancer. We will make special
particles called nanoparticles that will contain our newly developed SK1 inhibitors together with a standard
docetaxel chemotherapy drug. These nanoparticles will ensure the targeted delivery of the drugs to the
tumour, SK1 inhibitors will then 'weaken' the prostate cancer cells and allow docetaxel to act with more
effectiveness. This approach will likely allow us to overcome resistance in the cancer to docetaxel.
Why are you proposing it?
Prostate cancer is now the most commonly diagnosed non-cutaneous (not affecting the skin) cancer in men
and is the second leading cause of cancer-related death in the UK claiming approximately 10,000 lives every
year. Unfortunately after initial therapy, up to 90% of patients with some subtypes of localised prostate cancer,
and virtually all patients with advanced disease, relapse. For these patients chemotherapy can be offered;
however docetaxel chemotherapy provides only a small survival advantage with a median period of less than 3
months. In this context, any slight improvement in response to docetaxel chemotherapy would be of clear
benefit and there is an urgent imperative to identify potential chemotherapy targets that might sensitize
prostate cells to taxane therapies.
We have previously shown that a lipid kinase SK1 is an oncogene that drives progression and resistance of
prostate cancer to chemotherapy. We have found that pharmacological targeting of SK1 may be beneficial for
cancer patients, as it has the potential for enhancing the effects of standard chemotherapies and
radiotherapies. However the absence of clinically useable SK1 inhibitors has limited the impact of these
findings for patients.
How are you proposing to do it?
We have used new computer modelling methods of drug design to discover new highly specific SK1 inhibitors.
Our preliminary data show that these compounds have excellent anticancer activity and demonstrate highlevel interplay with standard docetaxel therapy. Now we aim to develop a "nanoparticle within a nanoparticle"
model, which will deliver the combination of docetaxel and new SK1 inhibitors specifically to the prostate
tumours and mediate their release one after another to suppress prostate cancer resistance to chemotherapy.
How long will it take?
The estimated duration of the project is 36 months
What is the budget?
£250,000
Prostate Cancer UK is a registered charity in England and Wales (1005541) and in Scotland (SC039332). A company limited by guarantee registered number 2653887 (England and Wales).
What are the expected outcomes?
It is our hope that nanoparticles combining new SK1 inhibitors and standard chemotherapy will offer survival
benefit for patients with difficult to manage prostate cancer resistant to chemotherapy and will lead to a Phase
I trial within the remit of Norfolk and Norwich NHS trust.
How could it make a difference to the lives of men affected by prostate
cancer?
Currently docetaxel is "the last resort" for men with metastatic prostate cancer. However many patients
develop resistance to the drug. We hope that our new therapeutic modality will allow us to overcome this
resistance and provide survival advantage for these patients.
Please write a summary of the project in one sentence only.
We aim to make a new therapy for men with advanced/metastatic prostate cancer that will hopefully allow us
to overcome drug resistance and provide survival advantage for these patients.