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Targeting the IGF/PI3K/mTOR pathway and AXL/YAP1/TAZ pathways in primary bone cancer

Danh D Truong1, Salah-Eddine Lamhamedi-Cherradi1, Joseph A Ludwig1

  • 1Department of Sarcoma Medical Oncology, Division of Cancer Medicine, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.

Journal of Bone Oncology
|March 7, 2022
PubMed

Insights

Primary bone cancers (PBCs) like Ewing sarcoma, osteosarcoma, and chondrosarcoma share common signaling pathways. Research highlights the IGF/PI3K/mTOR and AXL/YAP/TAZ pathways and emerging drug candidates for treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Primary bone cancers (PBCs) encompass aggressive, metastatic tumors such as Ewing sarcoma, osteosarcoma, and chondrosarcoma, predominantly affecting children and young adults.
  • These distinct sarcoma subtypes share common signaling pathways crucial for tumor progression, metastasis, and survival.

Purpose of the Study:

  • To review the roles of the IGF/PI3K/mTOR and AXL/YAP/TAZ pathways in promoting primary bone cancers.
  • To highlight drug candidates targeting these pathways currently under clinical investigation.

Main Methods:

  • Literature review of scientific publications and clinical trial data.
  • Analysis of signaling pathway involvement in PBC pathogenesis and progression.

Main Results:

  • The IGF/PI3K/mTOR and AXL/YAP/TAZ pathways are implicated in oncogenesis, cell fate, differentiation, metastasis, and drug resistance in PBCs.
  • Numerous small molecule inhibitors and antibody drug-conjugates targeting these pathways are in clinical trials.

Conclusions:

  • Targeting the IGF/PI3K/mTOR and AXL/YAP/TAZ pathways presents a promising therapeutic strategy for primary bone cancers.
  • Further clinical investigation of emerging drug candidates is warranted to improve treatment outcomes for PBC patients.
Keywords:
AXLBone cancerChondrosarcomaEwing sarcomaIGF-1ROsteosarcomaPI3KmTOR

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