Towards functional precision oncology with human organoids

Functional precision oncology is an approach that enables the provision of immediately translatable, personalised information to establish disease vulnerabilities and treatment options. Information is obtained from direct perturbations of tumour-derived living cells, which has become a complementary strategy to genomics-based precision medicine.1van de Haar J Ma X Ooft SN et al.Codon-specific KRAS mutations predict survival benefit of trifluridine/tipiracil in metastatic colorectal cancer.Nat Med. 2023; 29: 605-614Crossref PubMed Scopus (8) Google Scholar Tumour heterogeneity has facilitated the recognition of the need for personalised methods to improve therapeutic outcomes, and holds the potential for individualised cancer care.2Dekkers JF Alieva M Cleven A et al.Uncovering the mode of action of engineered T cells in patient cancer organoids.Nat Biotechnol. 2023; 41: 60-69Crossref Scopus (24) Google Scholar This strategy has become a powerful tool for assessing drug sensitivity and proposing novel therapeutic options or re-challenges in a personalised manner, attributable to the stable preservation of key characteristics (genetic, phenotypic, behavioural, etc) of original tumours, and of precise genomic and environmental manipulation.3Sun Y Revach OY Anderson S et al.Targeting TBK1 to overcome resistance to cancer immunotherapy.Nature. 2023; 615: 158-167Crossref Scopus (12) Google Scholar Given the potential to accurately generalise intratumoural and intertumoural heterogeneity, elimination of the technical variability that accompanies organotypic models is essential to build reproducible platforms that accelerate translatable insights into personalised management.4Jacob F Salinas RD Zhang DY et al.A patient-derived glioblastoma organoid model and Biobank recapitulates inter- and intra-tumoral heterogeneity.Cell. 2020; 180: 188-204Summary Full Text Full Text PDF PubMed Scopus (405) Google Scholar Furthermore, more clinical trials will be needed to evaluate the clinical implementation of cancer organoids, thus maximally benefiting future translational research. We declare no competing interests. This Correspondence was funded by the Guangzhou Municipal Science and Technology Bureau Grant (202102020162 awarded to ZW) and the National Natural Science Foundation of China (81901578 awarded to ZW).