Anti-angiogenesis target therapy for advanced osteosarcoma

Abstract

Osteosarcomas (OS), especially those with metastatic or unresectable disease, have limited treatment options. The greatest advancement in treatments occurred in the 1980s when multi-agent chemotherapy, including doxorubicin, cisplatin, high-dose methotrexate, and, in some regimens, ifosfamide, was demonstrated to improve overall survival compared with surgery alone. However, standard chemotherapeutic options have been limited by poor response rates in patients with relapsed or advanced cases. It has been reported that VEGFR expression correlates with the outcome of patients with osteosarcoma and circulating VEGF level has been associated with the development of lung metastasis. At present, it seems to us that progress has not been made since Grignani reported a phase II cohort trial of sorafenib and sorafenib combined with everolimus for advanced osteosarcoma, which, in a sense, have become a milestone as a second-line therapy for osteosarcoma. Although the recognization of muramyltripepetide phosphatidyl-ethanolamine has made some progress based on its combination with standard chemotherapy, its effect on refractory cases is controversial. Personalized comprehensive molecular profiling of high-risk osteosarcoma up to now has not changed the therapeutic prospect of advanced osteosarcoma significantly. Thus, how far have we moved forward and what therapeutic strategy should we prefer for anti-angiogenesis therapy? This review provides an overview of the most updated anti-angiogenesis therapy in OS and discusses some clinical options in order to maintain or even improve progression-free survival.

Establishment of three‐dimensional canine osteosarcoma cell lines showing vasculogenic mimicry and evaluation of biological properties after treatment with 17‐AAG

“…VM represents one of the major causes for the development of resistance to anti‐angiogenic therapy in solid tumours, and it seems that VM is dependent on the most common pro‐angiogenic factors . In particular, the mechanisms responsible for resistance to anti‐angiogenic therapy have been widely investigated in human OSA and several studies underlining the role of Hsp90 have been carried out …”

“…36,37 In particular, the mechanisms responsible for resistance to anti-angiogenic therapy have been widely investigated in human OSA and several studies underlining the role of Hsp90 have been carried out. 5,[38][39][40][41] In this respect, the development of drugs based on Hsp90 inhibition could be an important goal in cancer research because multiple proteins involved in tumour progression may be simultaneously inhibited. 42 We have previously showed that Hsp90 is over-expressed in canine OSA tissues, suggesting a role in tumour progression and that in vitro treatment with 17-AAG induced autophagy and apoptosis in D17 cell line.…”

The Anticancer Properties of Tanshinones and the Pharmacological Effects of Their Active Ingredients

“…There are eight members of the gene family: VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-E, VEGF-F, and placenta growth factor-1 (PIGF-1) and PIGF-2. It has many functions, including stimulating angiogenesis, recruiting new blood vessels, inflammation, and vascular permeability through angiogenic, which constitutes the most important signal pathway in tumor angiogenesis (Xie et al, 2017). In a recent study, Tan IIA dramatically suppressed; VEGF promoted the migration and tube formation of human endothelia progenitor cells through the phospholipase C (PLC), Akt, and JNK signaling pathways without cytotoxic effect .…”

<p>Anorexia, Hypertension, Pneumothorax, and Hypothyroidism: Potential Signs of Improved Clinical Outcome Following Apatinib in Advanced Osteosarcoma</p>

“…Vascular endothelial growth factor (VEGF) and its receptors (VEGFRs) play a critical role in angiogenesis in osteosarcoma. 1 All of the VEGFR-TKIs with a high specificity and strong affinity only had a median PFS of 4-6 months for refractory osteosarcoma, 2,3,5,27-29 suggesting an urgent need for a predictive marker that indicates benefits from VEGFR-TKI. The already explored potential predictive factors included patient-related factors, such as VEGFR gene polymorphisms; 30 tumor-related factors, such as microvascular density, serum VEGF level and VEGFR-2 expression; 31 and drug-related factors, such as treatment-induced hypertension and hand-foot syndrome.…”

“…The process of angiogenesis is crucial for osteosarcoma growth, invasiveness, and metastasis. 1 Anti-angiogenesis tyrosine kinase inhibitors (TKIs) are effective in prolonging progression-free survival (PFS) for advanced osteosarcoma that has progressed upon firstor second-line chemotherapy. 2,3 In a prospective study on apatinib for advanced osteosarcoma after the failure of traditional multimodal therapy (NCT02711007), apatinib reached 4-month PFS rate of 56.8% for advanced osteosarcoma [4][5][6][7] with a tolerable and manageable safety profile.…”