Stem Cells, Cancer and Metastasis
6-11 March 2011. Keystone Resort, Keystone, Colorado,
Organised by Richard J. Gilbertson (St Jude Children's
Research Hospital, USA) and Daniel A. Haber (Massachusetts General Hospital,
USA), this meeting focussed on understanding the cellular biology of cancer in
order to address important clinical problems.
The topics covered included techniques to detect and track
stem cells, investigating the cell of origin for different cancers, and
potential therapies for cancers that metastasise or are resistant to therapy.
Overall, the quality of the talks was excellent and several
topics had similarities to my project. I especially enjoyed Richard
Gilbertson's talk on homo- and heterogeneity which addressed why similar
tumours respond differently to the same treatment. I was interested to learn
that there is strong evidence that two separate types of cells can give rise to
the same classification of Medulloblastoma, a cerebellum tumour. These two
distinct cells of origin formed molecularly different tumours referred to as
Wnt subtype and SHH subtype. These two subtypes have mutations in their
corresponding pathways which lead to cancers forming in different regions of
the brain. MRI and computational analysis of overlapping gene expression
between the tumours and regions of expression in the brain validated this
argument by illustrating two distinct areas where these tumours form. These two
regions comprised of tumours arising in the 4th ventricle compared to those
that are attached to the dorsal brainstem. Remarkably, this may suggest that
the cell of origin for one subtype of Medulloblastoma, which are currently
known as cerebellum tumours, may in fact be tumours of the brainstem that
invade. I am studying intracranial germ cell tumours, and I am also
investigating the cell of origin for these tumours. Therefore, Richard
Gilbertson's talk helped me to develop my own project and gave me several ideas
to discuss with my supervisor.
The morning session of the third day focussed on cancer stem
cells, with a specific focus on breast cancer. Professor Max Wicha (University
of Michigan, USA) described the effects of stem cell directed chemotherapeutics
in the advanced and adjuvant setting i.e. during or post-treatment. Breast
cancers that express high levels of Her2 receptor have been previously shown to
be indicative of highly aggressive cancers. This aggressive nature of cancer is
hypothesised to be linked with Her2 because it is a growth factor receptor.
Following this finding, several therapies have been developed to target and
block the Her2 receptor and Trastuzumab, also known as Herceptin, is one such
drug. Interestingly however, it appears that tumours that are Her2 negative
respond to Trastuzumab with equal efficacy to Her2 positive cancers. I
initially thought this finding was counter-intuitive because blocking the Her2
receptor in normal cells should not have an effect on the entire cancer. However,
it is now hypothesised that the cancer stem cells are expressing high levels of
Her2 but the bulk of the tumour where the biopsy would have been taken are not.
Therefore, treatment is more effective because there is no cancer stem cell
population left to form another cancer. I found this talk fascinating even
though my research does not focus on either cancer stem cells or breast cancer.
He concluded with his plans for clinical trials to investigate therapies that
target cancer stem cells given in the adjuvant setting. To complement this, he
is also performing further studies involving the cancer stem cell mouse model
that he has developed.
During the whole meeting there were recurring themes
regarding cancer stem cells. One of these themes was the difficulty in finding
a consistent and specific marker for these cancer stem cells in order to better
understand their role in tumour formation and progression. Several different
labs had evidence that they had found such markers; however, these were often contradicted
by different labs. One of the inherent difficulties with these studies is that
samples of the cancers involved are difficult to obtain. During the final
session, all researchers had the opportunity to participate in an open
discussion about several of the themes during the conference, and this topic
was briefly addressed. I think the most practical suggestion was for each lab
to check all the potential markers against all of their own cancers. I agree
that this is the most unbiased way of validating other labs' evidence because
no one has a bias in validating their own marker.
Each evening for the first three evenings, researchers were
given the opportunity to present a poster on the work their labs are doing. The
poster I presented described the epigenetic differences between two types of
paediatric brain tumour; yolk sac tumours and germinomas. The researchers
interested in my poster ranged from scientists beginning to investigate
methylation, to specialists who offered feedback. This process of discussion
and feedback was valuable for my broader scientific understanding.
Some of the areas of research presented during the poster
sessions mirrored aspects of my work. It was very useful to discuss the
problems and solutions to some of the same experiments I am trying as this gave
me a new understanding as well as offering alternatives to other peoples'
Aside from the fantastic research at the meeting, the
beautiful scenery surrounding the accommodation and conference centre was home
to one of the best ski resorts in North America. The conference schedule
allowed for ample time to ski on one of 135 ski slopes at the resort. These
ranged from beginner slopes to some of the most difficult The Rocky Mountains
had to offer, and this was quite evident by the increasing number of arm and
leg braces as the conference proceeded!
In summary, the Keystone meeting allowed me to network with
potential future employers, examine other researchers' work, and mature my
scientific thinking. I enjoyed the conference enormously and I am very grateful
to BSCB, BSDB, and The Genetics Society to have been given the opportunity to
University of Nottingham