TY - JOUR
T1 - Targeting the IGF/PI3K/mTOR pathway and AXL/YAP1/TAZ pathways in primary bone cancer
AU - Truong, Danh D.
AU - Lamhamedi-Cherradi, Salah Eddine
AU - Ludwig, Joseph A.
N1 - Publisher Copyright:
© 2022 The Authors
PY - 2022/4
Y1 - 2022/4
N2 - Primary bone cancers (PBC) belong to the family of mesenchymal tumors classified based on their cellular origin, extracellular matrix, genetic regulation, and epigenetic modification. The three major PBC types, Ewing sarcoma, osteosarcoma, and chondrosarcoma, are frequently aggressive tumors, highly metastatic, and typically occur in children and young adults. Despite their distinct origins and pathogenesis, these sarcoma subtypes rely upon common signaling pathways to promote tumor progression, metastasis, and survival. The IGF/PI3K/mTOR and AXL/YAP/TAZ pathways, in particular, have gained significant attention recently given their ties to oncogenesis, cell fate and differentiation, metastasis, and drug resistance. Naturally, these pathways – and their protein constituents – have caught the eye of the pharmaceutical industry, and a wide array of small molecule inhibitors and antibody drug-conjugates have emerged. Here, we review how the IGF/PI3K/mTOR and AXL/YAP/TAZ pathways promote PBC and highlight the drug candidates under clinical trial investigation.
AB - Primary bone cancers (PBC) belong to the family of mesenchymal tumors classified based on their cellular origin, extracellular matrix, genetic regulation, and epigenetic modification. The three major PBC types, Ewing sarcoma, osteosarcoma, and chondrosarcoma, are frequently aggressive tumors, highly metastatic, and typically occur in children and young adults. Despite their distinct origins and pathogenesis, these sarcoma subtypes rely upon common signaling pathways to promote tumor progression, metastasis, and survival. The IGF/PI3K/mTOR and AXL/YAP/TAZ pathways, in particular, have gained significant attention recently given their ties to oncogenesis, cell fate and differentiation, metastasis, and drug resistance. Naturally, these pathways – and their protein constituents – have caught the eye of the pharmaceutical industry, and a wide array of small molecule inhibitors and antibody drug-conjugates have emerged. Here, we review how the IGF/PI3K/mTOR and AXL/YAP/TAZ pathways promote PBC and highlight the drug candidates under clinical trial investigation.
KW - AXL
KW - Bone cancer
KW - Chondrosarcoma
KW - Ewing sarcoma
KW - IGF-1R
KW - mTOR
KW - Osteosarcoma
KW - PI3K
UR - http://www.scopus.com/inward/record.url?scp=85125540925&partnerID=8YFLogxK
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U2 - 10.1016/j.jbo.2022.100419
DO - 10.1016/j.jbo.2022.100419
M3 - Article
C2 - 35251924
AN - SCOPUS:85125540925
SN - 2212-1374
VL - 33
JO - Journal of Bone Oncology
JF - Journal of Bone Oncology
M1 - 100419
ER -