RANKL blockade prevents and treats aggressive osteosarcomas. (Sci Transl Med. 2015, 7(317):317ra197.) Cancer 組別,主持人:黃柏憲

報告日期: 2017/04/28
報告時間: 5:10/6:00
報告學生: 翁閎楷(以英文報告)
講評老師: 許育祥
附件下載: 下載[1651-1487734189-1.pdf] 

RANKL blockade prevents and treats aggressive osteosarcoma

Chen Y, Di Grappa MA, Molyneux SD, McKee TD, Waterhouse P, Penninger JM, Khokha R

Sci Transl Med. 2015 Dec 9;7(317):317ra197. doi: 10.1126/scitranslmed.aad0295.

Speaker: Hung-Kai Weng (翁閎楷)

Commentator: Dr. Yu-Hsiang Hsu (許育祥老師)

Time: 17:10-18:00, Apr. 28th, 2017 (Fri.)

Place: Room 602

Abstract:

  Osteosarcoma (OS) is the most common primary malignant bone tumor, mainly affecting children and adolescents. For the past decades, the survival of patients with osteosarcoma was improved, but not so much. Till now, the mainstream treatments are still only surgical excision combined with neoadjuvant and adjuvant chemotherapy, which could let 5-year survival rate around 70%. In nonmetastatic tumor, 5-year survival rate even could reach 90%. However, 5-year survival rate dropped to only 20-25% in patients with metastatic disease and 50% in poor response to chemotherapy. In addition to current chemotherapy formulation, a new strategy to control aggressive tumor is the present urgent issue. Mutations in p53 and Rb are linked to the evolution of OS, and used to develop transgenic mouse models. Combined osteoblast-specific deletions of Rb, p53, and the protein kinase A (PKA) regulatory subunit Prkar1α genes in genetically engineered mouse models (GEMMs) generated aggressive osteosarcomas, characterized by PKA, RANKL, and osteoclast hyperactivity. Whole-body RANKL deletion greatly diminished osteosarcomagenesis. Although there was little effect in osteoblastic RANK deletion, osteoclastic RANK deletion delayed tumorigenesis and prolonged life span. Inactivation of osteoclastogenesis was associated with up-regulation of the tumor suppressor phosphatase and tensin homolog (PTEN). Further, the authors used these GEMMs to show that RANKL blockade with RANK-Fc improved survival and inhibited lung metastasis. Moreover, preemptive administration of RANK-Fc completely prevented tumorigenesis.

Reference:

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  2. Hung GY, Yen HJ, Yen CC, et al. Experience of pediatric osteosarcoma of the extremity at a single institution in Taiwan: prognostic factors and impact on survival. Ann Surg Oncol 2015;22:1080-7.