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Functional precision oncology using patient-derived assays: bridging genotype and phenotype
Allard W J van Renterghem1,2, Joris van de Haar1,2, Emile E Voest3,4
1Division of Molecular Oncology and Immunology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Abstract:
Genomics-based precision medicine has revolutionized oncology but also has inherent limitations. Functional precision oncology is emerging as a complementary approach that aims to bridge the gap between genotype and phenotype by modelling individual tumours in vitro. These patient-derived ex vivo models largely preserve several tumour characteristics that are not captured by genomics approaches and enable the functional dissection of tumour vulnerabilities in a personalized manner. In this Review, we discuss several examples of personalized functional assays involving tumour organoids, spheroids and explants and their potential to predict treatment responses and drug-induced toxicities in individual patients. These developments have opened exciting new avenues for precision oncology, with the potential for successful clinical applications in contexts in which genomic data alone are not informative. To implement these assays into clinical practice, we outline four key barriers that need to be overcome: assay success rates, turnaround times, the need for standardized conditions and the definition of in vitro responders. Furthermore, we discuss novel technological advances such as microfluidics that might reduce sample requirements, assay times and labour intensity and thereby enable functional precision oncology to be implemented in routine clinical practice.
Insights
Functional precision oncology uses patient-derived tumor models to complement genomics, predicting treatment responses. Overcoming barriers like assay standardization and speed is key for clinical integration.
Area of Science:
- Oncology
- Genetics
- Translational Medicine
Background:
- Genomics-based precision medicine has transformed cancer treatment but has limitations.
- Functional precision oncology offers a complementary approach by modeling individual tumors ex vivo.
- Patient-derived ex vivo models capture tumor characteristics beyond genomics, enabling functional analysis.
Purpose of the Study:
- To review personalized functional assays in oncology, including organoids, spheroids, and explants.
- To discuss the potential of these assays in predicting patient treatment responses and toxicities.
- To identify barriers to clinical implementation and explore technological advancements.
Main Methods:
- Review of personalized functional assays using patient-derived tumor organoids, spheroids, and explants.
- Discussion of the potential of these models to predict treatment outcomes and drug toxicities.
- Analysis of challenges including assay success rates, turnaround times, standardization, and defining in vitro responders.
Main Results:
- Functional assays can model individual tumors ex vivo, preserving key characteristics.
- These models show potential for predicting treatment responses and drug toxicities.
- Technological advances like microfluidics may enhance feasibility and reduce resource demands.
Conclusions:
- Functional precision oncology complements genomics, offering insights where genomic data is insufficient.
- Overcoming implementation barriers is crucial for routine clinical adoption.
- Technological innovations are paving the way for broader application of functional precision oncology.
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