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Preclinical Childhood Sarcoma Models: Drug Efficacy Biomarker Identification and Validation
Brian Geier1, Dias Kurmashev2, Raushan T Kurmasheva2
1Center for Childhood Cancer and Blood Diseases, Nationwide Children's Hospital , Columbus, OH , USA.
Abstract:
Over the past 35 years, cure rates for pediatric cancers have increased dramatically. However, it is clear that further dose intensification using cytotoxic agents or radiation therapy is not possible without enhancing morbidity and long-term effects. Consequently, novel, less genotoxic, agents are being sought to complement existing treatments. Here, we discuss preclinical human tumor xenograft models of pediatric cancers that may be used practically to identify novel agents for soft tissue and bone sarcomas, and "omics" approaches to identifying biomarkers that may identify sensitive and resistant tumors to these agents.
Insights
Pediatric cancer cure rates are rising, but further treatment intensification is limited. New, less toxic agents are needed, and preclinical models and omics approaches can help identify them for sarcomas.
Area of Science:
- Oncology
- Pediatric Oncology
- Cancer Research
Background:
- Pediatric cancer cure rates have significantly improved over the last 35 years.
- Further dose escalation of current cytotoxic agents or radiation therapy is limited by increased morbidity and long-term adverse effects.
- There is a critical need for novel, less genotoxic therapeutic agents to augment existing pediatric cancer treatments.
Purpose of the Study:
- To review the utility of preclinical human tumor xenograft models for identifying novel therapeutic agents for pediatric soft tissue and bone sarcomas.
- To explore the application of "omics" approaches in identifying biomarkers for predicting tumor sensitivity or resistance to novel agents.
- To discuss strategies for advancing the development of less toxic therapies for pediatric cancers.
Main Methods:
- Discussion of preclinical human tumor xenograft models relevant to pediatric sarcomas.
- Review of "omics" technologies (genomics, proteomics, etc.) for biomarker discovery.
- Analysis of strategies for integrating preclinical models and biomarker data.
Main Results:
- Preclinical xenograft models provide a practical platform for evaluating novel therapeutic candidates in pediatric cancers.
- "Omics" approaches can identify molecular signatures associated with treatment response.
- Biomarker identification is crucial for personalizing treatment and improving outcomes.
Conclusions:
- Novel, less genotoxic agents are essential for improving pediatric cancer treatment outcomes.
- Preclinical xenograft models and "omics" strategies are vital tools for discovering and validating these new agents.
- Integrating these approaches will facilitate the development of more effective and less toxic therapies for pediatric soft tissue and bone sarcomas.
