Advances in the development of chordoma models for drug discovery and precision medicine
Robert L Walker1, Francis J Hornicek1, Zhenfeng Duan1
1Department of Orthopedic Surgery, Sarcoma Biology Laboratory, Sylvester Comprehensive Cancer Center, The University of Miami Miller School of Medicine, Papanicolaou Cancer Research Building, 1550 NW, 10th Avenue, Miami, FL 33136, USA.
Abstract:
Chordomas are malignant bone tumors that arise from remnants of the notochord. These tumors are generally slow-growing, locally aggressive, and invasive. Chordomas are typically resistant to conventional chemo- and radiotherapy. The clinical management of this disease is very challenging, usually, treatment is surgical resection, which may be combined with radiotherapy. Although chordomas have undergone histologic and genetic analysis, the molecular mechanisms that drive their pathogenesis and resistance are still largely unknown. For many years this could be attributed to the lack of accurate and reliable in vitro and in vivo tumor models. Yet, over the past decade, many efforts have been made to prioritize the generation of useful chordoma cell lines, and tumor models that have shed more light on this malignancy and have made efficacious drug discovery a greater possibility. This review summarizes and discusses recent enhancements and improvements made to generate useful chordoma models and their applications in drug discovery and precision medicine.
Insights
Chordomas are rare malignant bone tumors. Recent advancements in generating chordoma models are improving our understanding of their molecular drivers and enabling new drug discovery for precision medicine.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Chordomas are rare, locally aggressive malignant bone tumors originating from notochordal remnants.
- These tumors exhibit resistance to conventional therapies, posing significant clinical management challenges.
- Understanding the molecular pathogenesis and resistance mechanisms is crucial for effective treatment.
Purpose of the Study:
- To review recent advancements in developing accurate in vitro and in vivo chordoma models.
- To discuss the applications of these improved models in drug discovery and precision medicine.
Main Methods:
- Review of literature on chordoma model generation and characterization.
- Analysis of studies utilizing chordoma models for therapeutic target identification.
Main Results:
- Significant progress has been made in generating reliable chordoma cell lines and animal models.
- These models provide better platforms for studying chordoma biology and screening potential therapeutics.
- Recent models offer insights into the molecular drivers of chordoma pathogenesis and treatment resistance.
Conclusions:
- Enhanced chordoma models are critical for deciphering tumor biology and resistance mechanisms.
- These models are accelerating the development of novel therapeutic strategies and precision medicine approaches for chordoma.
- Continued development and utilization of these models hold promise for improving patient outcomes.
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