Why we funded it
By selecting different drugs to use at different times during
this treatment regime Professor McKeown hopes to design new methods
for treating androgen-dependent prostate cancer that should improve
survival times. Other information gained from the study will be
used to identify new targets for killing prostate cancer cells.
Scientific title
Understanding prostate tumour response to bicalutamide can lead
to improved treatment regimens
Research project summary
When men are first diagnosed with prostate cancer they often
have a tumour that requires a hormone (androgen) to stimulate their
growth. Consequently the patients are often treated with a drug
that blocks the effects of androgen on the tumour cells; this is
called androgen ablation therapy (AAT). Unfortunately we know that
it will only be successful in a proportion of patients before the
tumour returns in a form that is no longer sensitive to androgens.
This type of 'advanced' tumour is much less sensitive to a wide
range of treatments and has often spread to other parts of the
patient's body. This research project is to investigate new
combination drug therapies for their effectiveness against
hormone-dependent prostate cancer.
The drug bicalutamide is a form of AAT treatment during which
the tumours become hypoxic (have very low oxygen levels), which
leads to development of resistance to treatment and re-growth of
cancer cells (link to further info below). Currently bicalutamide
is rarely used in combination with other drugs except Zoladex which
has severe side effects. Our studies aim to prove that prostate
tumour control is achievable using bicalutamide combined with other
less toxic drugs. We propose to test a number of different
schedules using our knowledge of the physiological changes caused
by bicalutamide to inform new methods to trial drug combinations in
patients.
Professor McKeown and her research team have well characterised
animal models which demonstrate the changes in oxygen levels as
described, they will use a carefully planned regime of drugs to
target the tumour specific changes as they take place. (link to
further info below) This project will investigate a number of new
methods designed to treat androgen-dependent prostate cancer that
should enhance average survival for some considerable time.
Understanding the physiological and molecular changes caused by
bicalutamide could lead to the design of new treatment combinations
that could significantly improve tumour control. With the correct
schedule it could add several months (possibly even years) to the
effective life span of treatments - the drug combinations should be
much more effective in killing the tumour cells before they become
insensitive to treatment. Both of the drugs that the study
will combine with bicalutamide act on characteristics only found in
tumours. This means that they have very few side effects, so it is
likely that the combinations proposed would only show a limited
increase in toxicity to the patient as compared to bicalutamide
alone.
For further info read here...