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Angiogenesis
Erschienen in: Angiogenesis 3/2020

24.04.2020 | Review Paper

Apatinib as targeted therapy for advanced bone and soft tissue sarcoma: a dilemma of reversing multidrug resistance while suffering drug resistance itself

verfasst von: Qian-Kun Yang, Tong Chen, Shi-Qi Wang, Xiao-Jing Zhang, Zhong-Xiang Yao

Erschienen in: Angiogenesis | Ausgabe 3/2020

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Abstract

Bone and soft tissue sarcomas are rare malignant tumors originated from mesenchymal tissues. They harbor more than 50 distinct subtypes and differ in pathological features and clinical courses. Despite the significant improvements in modern multi-modality treatment, the outcomes and overall survival rates remain poor for patients with advanced, refractory, metastatic, or relapsed diseases. The growth and metastasis of bone and soft tissue sarcoma largely depend on angiogenesis, and VEGF/VEGFR pathway is considered as the most prominent player in angiogenesis. Therefore, blockade of VEGF/VEGFR pathways is a promising therapeutic strategy to retard neovascularization. Several VEGFR inhibitors have been developed and revealed their favorable anti-neoplastic effects in various cancers, but such desirable anti-tumor effects are not obtained in advanced sarcomas because of multiple reasons, such as drug tolerance, short duration of response, and severe adverse effects. Fortunately, preclinical and clinical studies have indicated that apatinib is a novel promising VEGFR2 inhibitor showing potent anti-angiogenic and anti-neoplastic activities in advanced sarcomas. Especially, apatinib has showed notable characteristics in multidrug resistance reversal, tumor regression, vascular normalization, immunosuppression alleviation, and enhancement of chemotherapeutic and radiotherapeutic effects. However, apatinib also gets struck in dilemma of reversing multidrug resistance of chemotherapeutic agents while suffering drug resistance itself, and several difficulties should be tackled before full use of apatinib. In this review, we discuss the outstanding characteristics and main predicaments of apatinib as targeted therapy in advanced sarcomas.

Graphic abstract

Bone and soft tissue sarcomas are rare but malignant tumors originated from mesenchymal tissues. They harbor more than 100 distinct subtypes and differ in features of pathologies and clinical courses. Despite the significant improvements in modern multi-modality treatment, the outcomes and overall survival rates remain poor for patients with advanced, refractory, metastatic, or relapsed lesions. The growth and metastasis of bone and soft tissue sarcoma largely depend on angiogenesis and VEGF/VEGFR pathways play a pivotal role in angiogenesis. Therefore, blockade of VEGF/VEGFR pathways is a promising therapeutic strategy. Several VEGFR inhibitors have been developed and verified in clinical trials but with unfavorable outcomes. Fortunately, preclinical studies and clinical trials have indicated that apatinib is a novel promising VEGFR2 inhibitor showing potent anti-angiogenic and anti-neoplastic activities in advanced sarcomas. Actually, apatinib has showed notable characteristics in multidrug resistance reversal, tumor regression, vascular normalization, immunosuppression alleviation, enhancement of chemotherapeutic and radiotherapeutic effects. However, apatinib also gets struck in dilemma of reversing multidrug resistance of chemotherapeutic agents while suffering drug resistance itself, and several difficulties should be tackled before full use of apatinib. In this review, we discuss the outstanding characteristics and main predicaments of apatinib as targeted therapy in advanced sarcomas.
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Metadaten
Titel
Apatinib as targeted therapy for advanced bone and soft tissue sarcoma: a dilemma of reversing multidrug resistance while suffering drug resistance itself
verfasst von
Qian-Kun Yang
Tong Chen
Shi-Qi Wang
Xiao-Jing Zhang
Zhong-Xiang Yao
Publikationsdatum
24.04.2020
Verlag
Springer Netherlands
Erschienen in
Angiogenesis / Ausgabe 3/2020
Print ISSN: 0969-6970
Elektronische ISSN: 1573-7209
DOI
https://doi.org/10.1007/s10456-020-09716-y

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