Download BRIGHT BLUE Funding Update August 2015

BRIGHT BLUE
Funding Update
August 2015
Anne Johnston
Why our partnership matters
Hugo was diagnosed with neuroblastoma when he
was just 9 months old and at six years of age is still
living with his cancer. He is currently recovering from
surgery to remove most of a tumour that invaded his
spinal column.
•
Cancer is the largest killer of children from
disease in Australia
•
More than 650 children are diagnosed in
Australia each year and sadly, nearly 3 children
will die from this terrible disease
•
While the overall survival rate has increased
from zero 60 years ago to over 80 per cent
today, there are still some aggressive cancers
that have much lower survival rates
•
Neuroblastoma, for example, is a cancer that
only occurs in children and the majority
present with advanced stage aggressive
cancers. For these children the survival rate is
less than 50%
•
Even for children who survive, 70% of children
will suffer significant long term side effects due
to their treatment and 30% will have severe
medical problems as adults such as heart
conditions, infertility or secondary cancers
caused not by their original cancer but by their
treatment
RNA Sequencing Project Recap
•
Bright Blue has donated $295,000 to date to fund
an innovative new research project into the causes
of neuroblastoma and potential new treatments
•
40% of the cases of neuroblastoma have an
identified link with a particular protein that enables
the cancer to develop
•
However in 60% of the cases of neuroblastoma
there is no evidence of a link to this particular
protein, it is critical we understand better what the
other causes of neuroblastoma might be
•
Our project uses leading edge genome typing
technology (called RNA sequencing) to improve
identification of the specific genetic abnormalities
that are linked to neuroblastoma initiation, growth,
metastasis and resistance to treatment
•
Ultimately this will lead to a more personalised
approach to treatment of children with
neuroblastoma which means we can tailor
treatment to their specific genetic type - this is the
future for finding the cure
What has this project achieved?
•
Completed next-generation RNA sequencing in 6
patient neuroblastoma cell lines and 69
neuroblastoma tumour tissue samples.
•
This is the first time this number of neuroblastoma
tumours has undergone next generation RNA
sequencing in this country.
•
The information gathered from analysing such a
huge amount of data (each child’s tumour generates
over 46 gigabytes of data) will ultimately be used in
‘real-time’ on newly diagnosed children with
neuroblastoma to identify particular sub-groups to
which they belong, according to their tumour’s
molecular profile.
•
This information will eventually allow us to treat
each disease with the right combination of drugs,
helping to improve the outcome for children with
neuroblastoma.
•
We are extremely grateful for the funding from
Bright Blue that has allowed this vital neuroblastoma
research to take place, we have made some exciting
discoveries and are keen to continue this research.
Research Finding 1: RP1X
•
Sequencing has revealed that 3 genes are dramatically
abnormally expressed in patient neuroblastoma cell lines
•
One particular gene called RP1X (RNA which has never
been studied in normal human biology or disease) has
been found to:



be over expressed in a subset of neuroblastoma
tissues
induce neuroblastoma cell growth and survival
correlate with poor patient survival rates
•
We have screened 114 anticancer drugs to find the best
combinations to target RP1X. THZ1, a novel anticancer
drug discovered in 2014 and originally used for lung
cancer in adults, in combination with panobinostat, may
be effective in killing neuroblastoma cells while leaving
healthy cells alone
•
We have generated pairs of neuroblastoma cells
expressing high or low levels of RP1X which are being
xenografted into mice to test this combination of anticancer drugs
•
Successful completion of these experiments may identify
a new treatment option for children in this subset
Research Finding 2: IGF2BP1
•
Collaboration with Martin Luther University
confirms that our findings relating to another
particular gene in neuroblastoma (IGF2BP1)
also to:

be over expressed in a subset of
neuroblastoma tissues

induce neuroblastoma cell growth and
survival

correlate with poor patient survival rates
•
IGF2BP1 is known to have a role in controlling
the levels of other genes and has previously
been reported as a pro-cancer factor, but has
not previously been linked to neuroblastoma.
•
These findings suggest that inhibiting this
gene in tumours where the gene has been
altered may be a potential therapeutic strategy.
This research on IGF2BP1 has now been
published by the internationally renowned and
prestigious Journal of Clinical Oncology.
Research Finding 3: MYCN-AS
•
We have also identified another novel gene called MYCNAS, which has never previously been studied in normal
human biology or in any disease.
•
Our research shows MYCN-AS is considerably overexpressed in a specific subset of human neuroblastoma
tumours, and high levels of MYCN-AS leads to poor
patient survival.
•
We have screened anticancer drugs, and found that JQ1,
a novel agent discovered in 2010, considerably reduces
MYCN-AS expression, and induces neuroblastoma cell
death.
•
We have further screened 2,690 potential anticancer
drugs and have found that vincristine works best with
JQ1.
•
We have had strong results testing this drug
combination in our mouse model and are currently
analysing tumour tissues from the mice to work out how
the drugs specifically kill the neuroblastoma cells.
•
Successful completion of these experiments may
identify a new treatment option for children in this
subset
Next steps…
•
Once the entire set of neuroblastoma tumour
samples has been sequenced and analysed we
will have a clear picture of all the particular
genes that have been altered in specific groups
of neuroblastoma patients.
•
We will then evaluate whether these genes are
indeed neuroblastoma “drivers” in mice and
therefore valuable therapeutic targets, followed
by laboratory-based drug sensitivity testing on
cells harbouring these altered genes to identify
new treatment options for children with
aggressive neuroblastoma.
•
By identifying critical genes that are altered in
aggressive neuroblastoma tumours combined
with drugs that specifically target these genes,
enables the possibility of delivering truly
personalised medicine.
•
The importance of this research thus lies in the
potential of providing new and novel therapies
to neuroblastoma patients who would
otherwise have a dismal outcome
We are particularly excited about these
results that would not have been possible
without the state-of-the-art technology
being employed and funding provided by
Bright Blue.
The Future : Personalised
Medicine
 How will we reach 10 out of 10
survival?
 “one size does not fit all”
 Need to tailor treatment – from
thousands of potential drugs to one
patient, one cancer, one treatment
plan.
 Children’s Cancer Institute to be a
central hub for all oncology units in
children’s hospitals across Australia
 All children with aggressive or
relapse cancer samples sent to our
labs – we will sequence their
genome/DNA
 Screen to identify best possible
treatment course for that one child,
advise clinician to increase chance of
cure
The Future : Personalised Medicine
 How will we reach 10 out of 10
survival?
 “one size does not fit all”
 Need to tailor treatment – from
thousands of potential drugs to one
patient, one cancer, one treatment
plan.
 Children’s Cancer Institute to be a
central hub for all oncology units in
children’s hospitals across Australia
 All children with aggressive or
relapse cancer samples sent to our
labs – we will sequence their
genome/DNA
 Screen to identify best possible
treatment course for that one child,
advise clinician to increase chance of
cure
Current model of
neuroblastoma therapy
The Future: Personalised medicine for
the therapy of neuroblastoma
Why is this work so important?
•
60% of neuroblastoma cases develop
without understanding the causes.
•
Currently the only treatment options are
harsh and toxic to these patients
•
Next-generation RNA sequencing is the
most advanced technology in medical
research today
•
It is the most effective technology for
identifying and understanding the proteins
within these genes
•
Through this RNA sequencing research we
can expect to identify:
 More personalised treatment approach
 More effective treatment
 Better chance of survival
 Better quality of life
Thank you