Lumen Autumn 2017 - Flipbook - Page 26
story by Ian Williams
On the trail of a
cancer cure
Professor Wayne Tilley is the medical research
equivalent of a super sleuth. For more than 30 years
he’s been on the trail of two of Australia’s biggest
serial killers – breast and prostate cancer.
L
ike any piece of complex detective
work, there have been some false
leads and disappointments.
But with the support of his team at
the University of Adelaide’s Dame Roma
Mitchell Cancer Research Laboratories,
and with strong international partnerships,
brilliant progress is being made.
Breakthrough insights are being
achieved into better understanding both
diseases and finding more targeted and
effective treatments.
Wayne is Director of the Dame Roma
which is widely recognised as one of the
world’s leading centres for research into
breast and prostate cancer.
His particular focus has been on
the critical role of sex hormones and
their cellular mediators – specifically
androgen, progesterone and oestrogen
receptors – on the spread and control
of both cancers.
“The problem we face is there are
multiple subtypes of prostate and breast
cancers and we know that at a molecular
level tumours are incredibly different from
patient to patient,” says Wayne.
“One of the challenges of coming
up with a new therapy is being able to
identify those patients who will benefit
and to outsmart a disease which has the
ability to adapt and become resistant to
current treatments.”
Wayne enjoyed early success in the
late 1980s when he cloned the human
androgen receptor (AR) and mapped
its genetic structure. This was pivotal to
the development of new treatments that
target this critical driver of prostate cancer.
24 Lumen | Autumn 2017
Since then he’s been able to highlight
the role of AR in driving prostate cancer
and show how it can adapt following
androgen deprivation therapies to still
drive tumour growth.
This helps explain how tumours
become resistant to androgen
deprivation therapies in advanced
prostate cancer and progress to
a lethal stage.
“For example, we discovered that the
AR can mutate to accommodate low
levels of androgen,” says Wayne.
“Our current research is looking at
new ways of eliminating the activity of
AR through novel molecules that target
different parts of the receptor without
having to remove androgen.
“It’s quite exciting, because it also
has potential to eliminate debilitating
side-effects associated with
androgen deprivation.”
With more than 3000 men expected to
die from prostate cancer this year, new
discoveries of this nature are vital.
Wayne has been overseeing the
research program at the Dame
Roma Mitchell laboratories since they
opened in 2002.
While he’s made important inroads into
stopping prostate cancer, Wayne and
his team have been equally successful in
researching breast cancer, which claims
the lives of more than 3000 Australian
women every year.
Again, their revelations on the role
of sex hormones in breast cancer is
proving hugely beneficial.
They have shown that androgen – while
potentially bad for prostate cancer – can
actually counteract the proliferative effects
of estrogen, which is responsible for about
75 per cent of breast cancer.
“We were able to show in experimental
models that androgens can inhibit the
growth of breast cancer and that’s led to
smarter ways to target breast cancer,”
says Wayne.
In another potential game changer, the
Dame Roma team has been working with
Cancer Research UK (CRUK) Cambridge
Institute on using progesterone in the
management of advanced breast cancers
that are resistant to standard treatments.
It’s a controversial area because
some progestins – synthetic forms
of progesterone – have long been
considered harmful by increasing breast
cancer risk. However, many studies now
indicate that there is no increased risk
with bioidentical progesterone made
from plant material.
“There is a natural ‘crosstalk’ between
estrogen (ER) and progesterone (PR)
receptors that we strongly believe can be
exploited,” says Wayne.
“When used with tamoxifen or other
current ER target therapies, we hope
to improve on the existing hormone
therapies. We have clinical trials starting
this year in Australia and the UK to test
the hypothesis.
“Progesterone is well tolerated and
cheap, making it an attractive treatment
option, especially in third world countries.”
Of course, any major research project
deserves the occasional unexpected
breakthrough. Some good fortune came
Wayne’s way when his researchers
discovered a technique for keeping
tumours alive to test new treatments after
they’ve been removed from a patient.
