Dermatofibrosarcoma protuberans(DFSP), the most common dermal sarcoma, is a low-grade, slow growing fibroblastic malignant neoplasm that most frequently affects middle aged adults and is characterized by a high local ...Dermatofibrosarcoma protuberans(DFSP), the most common dermal sarcoma, is a low-grade, slow growing fibroblastic malignant neoplasm that most frequently affects middle aged adults and is characterized by a high local recurrence rate and a low propensity for metastasis. Wide surgical resection or Mohs micrographic surgery(MMS) are the preferred approaches for localized disease, while radiation therapy is warranted for inoperable disease or for cases with positive margins where re-excision is not possible. DFSP is generally regarded as refractory to conventional chemotherapy. Treatment options for systemic disease were limited until the discovery of a unique translocation, t(17;22)(q22;q13)(COL1A1;PDGFB) found in a majority of cases. In recent years, imatinib, a PDGFβR, ABL and KIT inhibitor, has revolutionized systemic therapy in DFSP. In this review, we summarize the epidemiological, clinical, histological and genetic characteristics of DFSP and update the readers on its current management.展开更多
Historical overview of the treatment for advanced gastrointestinal stromal tumors(GISTs)GISTs represent a relatively rare entity;however,GISTs are still the most common mesenchymal neoplasm in the gastrointestinal tra...Historical overview of the treatment for advanced gastrointestinal stromal tumors(GISTs)GISTs represent a relatively rare entity;however,GISTs are still the most common mesenchymal neoplasm in the gastrointestinal tract.The majority of GISTs express the transmembrane receptor,KIT,a product of the KIT proto-oncogene that can lead to uncontrolled cell proliferation and resistance to apoptosis1-3.展开更多
Pazopanib is the first and only tyrosine kinase inhibitor currently approved for the treatment of multiple histological subtypes of soft tissue sarcoma(STS).Initially developed as a small molecule inhibitor of vascula...Pazopanib is the first and only tyrosine kinase inhibitor currently approved for the treatment of multiple histological subtypes of soft tissue sarcoma(STS).Initially developed as a small molecule inhibitor of vascular endothelial growth factor receptors,preclinical work indicates that pazopanib exerts an anticancer effect through the inhibition of both angiogenic and oncogenic signaling pathways.Following the establishment of optimal dosing and safety profiles in early phase studies and approval for the treatment of advanced renal cell carcinoma,pazopanib was investigated in STS.A landmark phase III randomized study demonstrated improved progression-free survival with pazopanib compared to that with placebo in pretreated patients with STS of various subtypes.The efficacy of pazopanib in specific STS subtypes has been further described in real-world-based case series in both mixed and subtype-specific STS cohorts.At present,there are no clinically validated predictive biomarkers for use in selecting patients with advanced STS for pazopanib therapy,limiting the clinical effectiveness and cost-effectiveness of the drug.In this review,we summarize the preclinical and clinical data for pazopanib,outline the evidence base for its effect in STS and explore reported studies that have investigated putative biomarkers.展开更多
基金support from the NIHR Royal Marsden/ICR Biomedical Research Center
文摘Dermatofibrosarcoma protuberans(DFSP), the most common dermal sarcoma, is a low-grade, slow growing fibroblastic malignant neoplasm that most frequently affects middle aged adults and is characterized by a high local recurrence rate and a low propensity for metastasis. Wide surgical resection or Mohs micrographic surgery(MMS) are the preferred approaches for localized disease, while radiation therapy is warranted for inoperable disease or for cases with positive margins where re-excision is not possible. DFSP is generally regarded as refractory to conventional chemotherapy. Treatment options for systemic disease were limited until the discovery of a unique translocation, t(17;22)(q22;q13)(COL1A1;PDGFB) found in a majority of cases. In recent years, imatinib, a PDGFβR, ABL and KIT inhibitor, has revolutionized systemic therapy in DFSP. In this review, we summarize the epidemiological, clinical, histological and genetic characteristics of DFSP and update the readers on its current management.
文摘Historical overview of the treatment for advanced gastrointestinal stromal tumors(GISTs)GISTs represent a relatively rare entity;however,GISTs are still the most common mesenchymal neoplasm in the gastrointestinal tract.The majority of GISTs express the transmembrane receptor,KIT,a product of the KIT proto-oncogene that can lead to uncontrolled cell proliferation and resistance to apoptosis1-3.
文摘Pazopanib is the first and only tyrosine kinase inhibitor currently approved for the treatment of multiple histological subtypes of soft tissue sarcoma(STS).Initially developed as a small molecule inhibitor of vascular endothelial growth factor receptors,preclinical work indicates that pazopanib exerts an anticancer effect through the inhibition of both angiogenic and oncogenic signaling pathways.Following the establishment of optimal dosing and safety profiles in early phase studies and approval for the treatment of advanced renal cell carcinoma,pazopanib was investigated in STS.A landmark phase III randomized study demonstrated improved progression-free survival with pazopanib compared to that with placebo in pretreated patients with STS of various subtypes.The efficacy of pazopanib in specific STS subtypes has been further described in real-world-based case series in both mixed and subtype-specific STS cohorts.At present,there are no clinically validated predictive biomarkers for use in selecting patients with advanced STS for pazopanib therapy,limiting the clinical effectiveness and cost-effectiveness of the drug.In this review,we summarize the preclinical and clinical data for pazopanib,outline the evidence base for its effect in STS and explore reported studies that have investigated putative biomarkers.
