2 research outputs found
A review of clinical and molecular prognostic factors in osteosarcoma
Traditional prognostic determinants in osteosarcoma
have included demographics (age, sex), tumour
size, site, stage, and the response to chemotherapy. Many of
these are determined using varying techniques and units of
measurement, which can make comparison between studies
diYcult. The absence of survival diVerence between limb
sparing surgery and amputation has been repeatedly demonstrated
in primary disease, and even in the setting of
pathological fracture. On the other hand, there is still some
controversy over the existence of increased local recurrence
for limb-sparing surgery, and the implications of this. Commonly
used prognostic determinants such as metastases,
and response to chemotherapy enable a high degree of
prognostic accuracy but usually at a late stage in the course
of disease. Leading on from this, there is a need to uncover
molecular pathways with speciWc inXuence over osteosarcoma
progression to facilitate earlier treatment changes.
Some important pathways are already being deWned, for
example the association of CXCR4 with metastases on presentation,
the likelihood of doxorubicin resistance with positive
P-glycoprotein, and the reduced survival prediction of
over expressed survivin. It is anticipated that the future of
osteosarcoma treatment will involve treatment tailored to
the molecular proWle of tumours at diagnosis, adjuvant therapy
directed towards dysfunctional molecular pathways
rather than the use of cytotoxics, and a more standardised
approach to the measurement of clinical prognostic factors
Osteosarcoma Development and Stem Cell Differentiation
Osteosarcoma is the most common nonhematologic malignancy of bone in children and adults. The peak incidence occurs in the second decade of life, with a smaller peak after age 50. Osteosarcoma typically arises around the growth plate of long bones. Most osteosarcoma tumors are of high grade and tend to develop pulmonary metastases. Despite clinical improvements, patients with metastatic or recurrent diseases have a poor prognosis. Here, we reviewed the current understanding of human osteosarcoma, with an emphasis on potential links between defective osteogenic differentiation and bone tumorigenesis. Existing data indicate osteosarcoma tumors display a broad range of genetic and molecular alterations, including the gains, losses, or arrangements of chromosomal regions, inactivation of tumor suppressor genes, and the deregulation of major signaling pathways. However, except for p53 and/or RB mutations, most alterations are not constantly detected in the majority of osteosarcoma tumors. With a rapid expansion of our knowledge about stem cell biology, emerging evidence suggests osteosarcoma should be regarded as a differentiation disease caused by genetic and epigenetic changes that interrupt osteoblast differentiation from mesenchymal stem cells. Understanding the molecular pathogenesis of human osteosarcoma could ultimately lead to the development of diagnostic and prognostic markers, as well as targeted therapeutics for osteosarcoma patients