Cancer Research - Europa

EuroBoNeT
European Network to Promote Research
into Uncommon Cancers in Adults
and Children: Pathology, Biology
and Genetics of Bone Tumours
Summary
Primary bone tumours are rare, accounting for ~0.2 % of the
cancer burden. Children and young adolescents are frequently
aff ected. The aggressiveness of these tumours has
a major impact on morbidity and mortality. Though progress
has been made in pathological and genetic typing, the aetiology
is largely unknown. Advances in therapeutic approaches
have increased survival rates, but a signifi cant numbers
of patients (~40 %) still die. Within the EuroBoNeT, staff
exchange, share of material and technologies, as well as the
organisation of training courses, will be used to increase and
disseminate knowledge of primary bone tumours. Exchange
of material, standard operating protocols, and the use of
technology platforms will enable us to obtain statistically
signifi cant datasets. A joint programme will contribute in
obtaining molecular portraits of tumours, separated into four
research lines: RL1: cartilaginous tumours; RL2: osteogenic
tumours and related sarcomas; RL3: osteoclastogenesis and
giant cell tumours of bone; and RL4: the Ewing family of
tumours. The tumours will be examined by genome-wide
expression, genomic aberration studies, and specifi c hypothesis-driven
approaches (RNA/protein expression and
mutation analysis). In vitro studies will be used to obtain
knowledge of normal growth and diff erentiation, and this
may help to identify markers for malignant transformation
and/or progression, as well as identifi cation of therapeutic
targets. Dissemination of knowledge will be achieved by
training courses on bone and soft tissue pathology. This is
essential since patients do not normally present themselves
at centres, and it is important to share such knowledge.
Problem
Bone sarcomas are rare and represent a group of cancers
that occur predominantly in children and young adults.
Intrinsic to their aggressive behaviour, these tumours are
lethal in about 40 % of patients despite modern multimodality
therapy. Although substantial progress has been made
over the last 10 years in understanding these tumours at the
biological, pathologic and genetic level, this has not been
translated into more eff ective therapies so far.
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Keywords | Bone tumour | chondrosarcoma | osteosarcoma | giant cell tumour of bone | Ewing’s sarcoma |
osteochondroma | Paget disease of bone | chondrogenesis | osteogenesis |
The 2002 WHO classifi cation recognises 32 diff erent entities
of bone tumours. Achieving signifi cant numbers to
study the diff erent types of bone tumours, which are already
rare as a group, is diffi cult. The research into these tumours
is often performed in relatively small research groups, which
are inherently hampered by the lack of availability of substantial
numbers of cases, as well as lacking a critical
technical and/or multidisciplinary mass. Interestingly, despite
their rareness, these tumours provide excellent examples for
unravelling oncogenic mechanisms.
The main problems are:
• collecting enough tumours to obtain reliable signifi cant
statistical results, also when comparing subtypes based on
locations, grade, etc.;
• since osteogenic and Ewing’s family of tumours are considered
orphan diseases, pharmaceutical companies will
not invest in developing new drugs;
• chemotherapeutic treatment can be toxic for the patient or
not eff ective, and there are no tools that predict which
patients are hypersensitive or which tumours are refractory;
• cartilaginous tumours are resistant to treatment other than
surgery. This can be mutilating and it is not always feasible
to remove the whole tumour (for instance in the pelvic
area);
• a small percentage of benign cartilaginous tumours develop
into malignant chondrosarcomas, but there are no clues
to recognising the ones that will deteriorate;
• the biological behaviour of giant cell tumours is variable and
cannot be predicted so far. In a small proportion of tumours,
synchronous or metachronous metastases develop;
• the biology of normal chondrogenesis and osteogenesis is
complex. A better under-standing of the pathways involved
could provide clues to the biology of bone tumours.
Aim
The above-mentioned major problems will be handled by
EuroBoNeT in the following ways:
• to overcome the spread of samples and lack of critical
technical and/or multidisciplinary mass in some of the
institutes, the main objective will be to reach integration
through sharing of samples, sharing of technologies and
incorporating all information gathered by the diff erent
partners. This will be done through staff exchange, core
facilities, a virtual BioBank and combining each others’
experimental results;
• the EuroBoNeT will characterise the tumours in the different
research lines by proteomics, genome-wide
expression analysis, and genomic array. This will provide
a large data set, which can be compared within and
between the diff erent tumour (sub)types. These data
will be used for:
• identifi cation of loci involved in conferring hypersensitivity
or chemotherapy resistance;
CANCER RESEARCH PROJECTS FUNDED UNDER THE SIXTH FRAMEWORK PROGRAMME