Anti-osteosarcoma Agents Research Articles

Human xenograft osteosarcoma models with spontaneous metastasis in mice: clinical relevance and applicability for drug testing

Osteosarcoma cells derived from patients have been isolated and subsequently cultured for the past 35 years. To date though, there have been no major breakthroughs in the development of a model for osteosarcoma that uses orthotopic implantation of human osteosarcoma cells and that closely emulates the clinical progression of this debilitating and fatal disease. Such a model is long overdue given the devastating demographics (second highest cause of cancer-related death in the paediatric age group) of the ailment and the lack of solid options for control, if not cure, for the disease, as it also is the most common primary tumour of bone. Only then can more robust R & D be undertaken in the search for efficacious anti-osteosarcoma agents. This review tackles this conundrum and lists the variety of models (that use human osteosarcoma cells) available and the types of studies performed with these.

Relation between cellular doxorubicin binding ability to nuclear DNA and histologic response to preoperative chemotherapy in patients with osteosarcoma.

Although chemosensitivity to antiosteosarcoma agents is the most important prognostic factor in human osteosarcoma, none of the many chemosensitivity tests reported previously are reliable and clinically useful. In this study, the authors investigated the reliability and clinical availability of doxorubicin (Adriamycin; Adria Laboratories, Columbus, OH) binding assay (ABA) as a new chemosensitivity test for osteosarcoma. Doxorubicin (adriamycin [ADM]) binding ability (%AB) to nuclear DNA in isolated osteosarcoma cells was assessed by ABA in 14 patients with primary osteosarcoma who were treated with preoperative chemotherapy containing ADM and 6 patients with relapsed osteosarcoma after intensive chemotherapy. Histologic responses to preoperative chemotherapy were evaluated by percentage of tumor necrosis (%necrosis). Four of the 14 patients with primary osteosarcoma had %AB > 80% (97.3+/-3.7%) and demonstrated good histologic responses (>90% of %necrosis) to preoperative chemotherapy, whereas the remaining 10 patients had %AB < 80% (38.9+/-21.0%) and demonstrated poor responses. Patients with recurrent osteosarcoma that was clinically evaluated to be resistant to previous chemotherapy also had low %AB (34.2+/-28.3%). Because the results of the current study revealed that ABA is useful for predicting chemosensitivity to chemotherapy with ADM as well as chemotherapy without ADM for patients with osteosarcoma, and because ABA technically is simple and results can be assessed rapidly, the authors conclude that ABA is a clinically useful chemosensitivity test for patients with osteosarcoma.