P-glycoprotein Expression in Osteosarcoma: A Basis for Risk-adapted Adjuvant Chemotherapy

Baldini, Nicola; Scotlandi, Katia; Serra, Massimo; Picci, P.; Bacci, Giacomo Maria; Sottili, S.; Campanacci, Mario

doi:10.2106/00004623-200002000-00033

Cited by 6 publications

(7 citation statements)

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“…They observed an association between increased tumoral expression of Pglycoprotein and worse event-free survival, including the development of metastases and sarcoma-related death [23]. They subsequently reported follow-up studies from their own institution corroborating these findings [24,25], but investigators at other centers have failed to reproduce their results [26].…”

Section: Discussionmentioning

confidence: 99%

P16 expression predicts necrotic response among patients with osteosarcoma receiving neoadjuvant chemotherapy

et al. 2012

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Section: Discussionmentioning

confidence: 99%

P16 expression predicts necrotic response among patients with osteosarcoma receiving neoadjuvant chemotherapy

et al. 2012

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“…Thus, there is a key link between clinical and molecular markers here, with the potential to select higher doses and diVerent combinations of chemotherapy earlier in the disease. In this regard, some particularly exciting Wndings linking molecular factors with speciWc disease events include; the association of CXCR4 with micrometastases at diagnosis (Laverdiere et al 2005), and the association of P-gp with resistance to doxorubicin (Baldini et al 1999). As further speciWc relationships are identiWed, it is likely that molecular markers will assume an increasing inXuence over future management of osteosarcoma by identifying tumours susceptible to speciWc molecular therapies.…”

Section: Discussionmentioning

confidence: 99%

“…In a retrospective study involving immunohistochemical analysis of paraYn-Wxed osteosarcoma samples (Baldini et al 1999) a signiWcant reduction in event-free survival in patients with tumours positive for P-gp was found. A group of 37 patients studied had received doxorubicin as a single agent post-operatively, and the expression of P-gp in this group, along with survival time, was compared with a group who received multi-agent chemotherapy.…”

Section: Upa/uparmentioning

confidence: 99%

A review of clinical and molecular prognostic factors in osteosarcoma

Clark

Dass

Choong

2007

J Cancer Res Clin Oncol

228

214

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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 difficult. The absence of survival difference 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 specific influence over osteosarcoma progression to facilitate earlier treatment changes. Some important pathways are already being defined, 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 profile 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.

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“…It was found that high levels of expressed P-gp in OS were associated with a significant reduction in the disease-free survival time. A study showed that P-gp was responsible for cancer cell resistance to doxorubicin as a single agent post-operatively, leading to an even worse survival time compared to patients with negative P-gp tumors [129]. However, P-gp does not correlate with the level of post-chemotherapy tumor necrosis [130], conflicting with the understanding of P-gp being involved in chemotherapy resistance by means of actively pumping these agents out of cells.…”

Section: Modern Molecular Markers and Potential Treatmentsmentioning

confidence: 99%

Osteosarcoma treatment: state of the art

Dass

Choong

et al. 2009

Cancer Metastasis Rev

255

224

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Osteosarcoma (OS) is a class of cancer originating from bone, mainly afflicting children or young adults. It is the second highest cause of cancer-related death in these age groups, mainly due to development of often fatal metastasis, usually in the lungs. Survival for these patients is poor despite the aggressive use of surgery, chemotherapy, and/or radiotherapy. Thus, new effective drugs and other forms of therapy are needed. This article reviews the biology and the state of the art management of OS. New experimental drugs and potential therapies targeting molecular pathways of OS are also discussed.

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P-glycoprotein Expression in Osteosarcoma: A Basis for Risk-adapted Adjuvant Chemotherapy

Cited by 6 publications

References 0 publications

P16 expression predicts necrotic response among patients with osteosarcoma receiving neoadjuvant chemotherapy

P16 expression predicts necrotic response among patients with osteosarcoma receiving neoadjuvant chemotherapy

A review of clinical and molecular prognostic factors in osteosarcoma

Osteosarcoma treatment: state of the art

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