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Updated: Dec 12, 2025

Three-Dimensional Bone Extracellular Matrix Model for Osteosarcoma
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Receptor Tyrosine Kinases in Osteosarcoma: 2019 Update

Edward M Greenfield1, Christopher D Collier2, Patrick J Getty3,4

  • 1Department of Orthopaedic Surgery, Indiana University School of Medicine and Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, USA. egreenf@iu.edu.

Advances in Experimental Medicine and Biology
|August 9, 2020
PubMed

Insights

Targeting multiple receptor tyrosine kinases (RTKs) is crucial for treating aggressive osteosarcoma and overcoming drug resistance. Identifying specific RTK combinations offers personalized therapeutic strategies for better clinical outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Osteosarcoma exhibits aggressive phenotypes often driven by multiple receptor tyrosine kinases (RTKs).
  • Resistance to single-target inhibitors and conventional chemotherapy necessitates novel therapeutic approaches.
  • Previous research identified specific RTKs as potential therapeutic targets in osteosarcoma.

Purpose of the Study:

  • To provide an update on the role of multiple RTK inhibition in osteosarcoma.
  • To review recent clinical studies involving multi-tyrosine kinase inhibitors (multi-TKIs) in osteosarcoma.
  • To highlight promising therapeutic targets for osteosarcoma treatment.

Main Methods:

  • In vitro phosphoproteomic and siRNA screening of 42 RTKs in osteosarcoma cell lines (LM7 and 143B).
  • Analysis of clinical studies on multi-TKIs for osteosarcoma treatment.

Main Results:

  • Multiple RTKs contribute to aggressive osteosarcoma phenotypes.
  • AXL, EPHB2, FGFR2, IGF1R, and RET were identified as promising therapeutic targets.
  • Combinations of RTK inhibition may overcome resistance mechanisms.

Conclusions:

  • Inhibition of multiple RTKs is essential for effective osteosarcoma treatment.
  • Targeting specific RTK combinations may lead to personalized therapeutic strategies.
  • Multi-TKI therapies show promise for improving clinical outcomes in osteosarcoma.
Keywords:
AXLEPHB2FGFR2IGF1RMulti-TKIsOsteosarcomaRETReceptor tyrosine kinases

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