Paul Span obtained his PhD on steroid metabolism from the Radboud University Nijmegen
in 1996. He is currently Associate Professor at the Department of Radiation Oncology.
Here, the experimental and clinical research is aimed at molecular and functional
imaging of tumors at the macroscopic and microscopic level in head and neck and breast
cancer, and more recently colorectal, lung and prostate cancer. An important objective
is the development of predictive profiles based on microenvironmental tumor characteristics
to ultimately provide a mechanistic basis for the optimization of treatments that
combine radiotherapy with novel biological modifiers and for development of patient
selection strategies. He is Basic Affairs Officer and member of the Steering Committee
of the PathoBiology Group of the European Organisation for Research and Treatment
Q Can you tell us a little about your career to date & how you came into oncology?
I studied Biology and actually did my master thesis on steroid metabolism in eels.
At that moment I knew I would rather continue my career investigating human subjects,
and was lucky enough to find a position at the Department of Chemical Endocrinology
of the Radboud University Medical Center in Nijmegen (The Netherlands). After my PhD
on prostate steroid metabolism, we started exploiting a large breast tumor biobank
that was available at the department, under the direction of professor Fred Sweep.
This biobank contained thousands of breast cancer tissues that had remained after
measuring estrogen receptor content for treatment selection for these patients. A
significant proportion of patients was treated with surgery, with or without radiotherapy,
but did not receive endocrine or chemotherapy. This made this cohort ideal for studies
into prognostic factors, in other words, factors that might predict how the disease
will progress irrespective of adjuvant treatment. Most of the prognostic and predictive
factors we have since identified turned out to be hypoxia related, eventually leading
to me now working at the Radiation Oncology department, which has a long-lasting expertise
Q What are you working on at the moment?
Our main interest at the moment is in how tumor cells are capable of surviving hypoxia,
more specifically the unfolded protein response, and autophagy. It is striking how
tumor cells develop mechanisms to counter the hostile microenvironment. The tumor
cells in hypoxic regions are also very resistant to radio- and chemotherapy. If we
would be able to counter the hypoxia resistance mechanisms of tumor cells, these cells
would die, leaving tumor cells that are relatively easy to target . We are venturing
into a number of – for us – new subjects, such as intracellular signaling pathways
 and metabolism . I think it is one of the great things about research that
you will always be learning new things. I am also very happy with the combination
of clinical, translational and basic research that I am able to do because of the
location of the laboratory within the clinical Radiation Oncology department, and
because of the excellent working relationship with the radiation oncologist and head
of the laboratory Dr Bussink.
Q You are involved with the Radboud & Nijmegen Breast Cancer Biobanks – can you tell
us a little about these?
As mentioned before, I started working in oncology mainly because of the availability
of a large clinical breast cancer tissue biobank. This was, however, a retrospective
biobank of breast cancer patients for which it was necessary to measure the estrogen
receptor (which leads to some bias), and who were treated very much differently compared
with current regimens. I have been working on setting up a prospective collection
of biomaterial, clinical data and informed consent from all breast cancer patients
at our medical center for some time, and we started doing this over a year ago. This
was possible because the Radboudumc initiated the Radboud biobank, facilitating much
of the infrastructure, and because a former PhD student of mine, Dr Manders, who now
leads this biobank.
Q What are you doing currently with the International Cancer Genome Consortium?
We contribute to the International Cancer Genome Consortium (ICGC) in the collection
of breast cancer samples for whole genome and RNA sequencing, methylation analyses
and such. This work has already been very fruitful, generating papers in high-ranking
journals [4,5], with many more publications to come. It is an example of how important
large, multinational, well-organized biobanks are. These biobanks will also prove
to be invaluable for future research, clinically or independently validating data
from other studies.
Q Can you tell us a little about your role with the European Organisation for Research
& Treatment of Cancer?
My work within the European Organisation for Research and Treatment of Cancer is performed
within the PathoBiology Group (PBG), which was founded – as the Receptor and Biomarker
Group – many years ago. The PBG is focused on linking translational research group
with clinical groups, for identification and validation of clinical biomarkers. Most
of the people within this group have known each other for many years, making it very
easy to set up collaborations for joint research.
Q What do you think are the biggest challenges for personalized medicine in oncology
at the moment?
The concept of personalized medicine is an important, but considering the temporal
and inter- and intra-tumor heterogeneity, difficult-to-obtain goal. Despite our recent
advances in understanding the effect of genomic instability, Darwinian selection of
treatment-resistant clones, the effect of the tumor microenvironment and so on, most
treatment regimens are given per protocol to large numbers of cancer patients irrespective
of their genotypes and phenotypes.
Q If you could, how would you go about addressing this?
Any advance we wish to make will depend on well-organized biobanks and trials, and
the public availability of all data that is subsequently obtained. Thus, I believe
it is crucial that biomaterials, clinical data and informed consent are obtained of
every patient, not only in trials but also in a ‘routine’ setting. Therefore I am
trying to extend our biobank initiative to other nonacademic hospitals within our
region. Furthermore, I applaud open access journal initiatives such as Future Science
OA. It will be absolutely crucial that all data are available for all researchers
if we are to move forward.
Q How do you see personalized medicine in oncology changing over the next 10 years?
Only a few biomarkers for selection of cancer patients for particular treatments have
so far made it to the clinic. I think we need to focus on not only identifying yet
more biomarkers, but also on using these in the clinic. Furthermore, we need to stay
realistic in our prediction of the future, as researchers have promised the eradication
of cancer several times in the past decades. I think we will certainly have made progress
in better selecting the right treatment for the right patient.
Q Finally, if you had unlimited resources at your disposal, what one piece of research
would you do, & why?
As might be expected considering what we talked about, I believe biobanking to be
crucial. I would be very much in favor of a continuation and extension of the ICGC
initiative, for instance, leading to a worldwide, well-defined biobank that is available
for all researchers. Furthermore, although not something that I do, I believe we should
make much more effort in actually using newly defined biomarkers in the clinic. Close
collaborations between (eel?) biologists and clinical doctors will remain necessary.