PDGF/PDGFR在骨肉瘤中的作用和“附加”策略。

Clinical Sarcoma Research Pub Date : 2018-08-02 eCollection Date: 2018-01-01 DOI:10.1186/s13569-018-0102-1
Jie Xu, Lu Xie, Wei Guo
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引用次数: 26

摘要

晚期骨肉瘤的新治疗选择仍然有限。血小板衍生生长因子(PDGF)/血小板衍生生长因子受体(PDGFR)通路通过直接自分泌刺激肿瘤细胞或旁分泌刺激肿瘤基质细胞,在骨肉瘤的发生转移过程中发挥重要作用。它促进血管生成以克服肿瘤微环境中的缺氧,并调节肿瘤间质液压力以控制其他药物的流入和流出。靶向PDGF/PDGFR通路是克服骨肉瘤耐药和改善患者预后的一种有前景的治疗方法。需要进一步的证据来确定详细的机制。在骨肉瘤和软组织肉瘤中,使用PDGF/PDGFR抑制剂作为单一药物的临床试验结果令人失望。然而,当与其他药物联合使用时,被称为“附加”策略,已证实在软组织肉瘤中具有协同抗肿瘤作用,应尝试在骨肉瘤中进行。
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PDGF/PDGFR effects in osteosarcoma and the "add-on" strategy.

New treatment options for advanced osteosarcoma have remained limited. The platelet-derived growth factor (PDGF)/platelet-derived growth factor receptor (PDGFR) pathway plays an important role in the development and metastasis of osteosarcoma, via either direct autocrine stimulation of tumor cells, or paracrine stimulation on tumor stromal cells. It promotes angiogenesis to overcome hypoxia in the tumor microenvironment, and modulates tumor interstitial fluid pressure to control the influx and efflux of other agents. Targeting the PDGF/PDGFR pathway is a promising therapeutic method to overcome drug resistance and improve patients' outcome in osteosarcoma. Further evidence is needed to define the detailed mechanism. Results from clinical trials using PDGF/PDGFR inhibitor as a single agent were disappointing, both in osteosarcoma and soft tissue sarcoma. However, when combined with other agents, named as "add-on" strategy, a synergistic antitumor effect has been confirmed in soft tissue sarcoma, and should be attempted in osteosarcoma.

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期刊介绍: Clinical Sarcoma Research considers for publication articles related to research on sarcomas, including both soft tissue and bone. The journal publishes original articles and review articles on the diagnosis and treatment of sarcomas along with new insights in sarcoma research, which may be of immediate or future interest for diagnosis and treatment. The journal also considers negative results, especially those from studies on new agents, as it is vital for the medical community to learn whether new agents have been proven effective or ineffective within subtypes of sarcomas. The journal also aims to offer a forum for active discussion on topics of major interest for the sarcoma community, which may be related to both research results and methodological topics.
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