AccScience Publishing / OR / Volume 2 / Issue 1 / DOI: 10.36922/OR026020002
REVIEW ARTICLE

Integrating patient-derived organoids and multi-omics to decode spatiotemporal therapeutic resistance

Cize Gao1 Jianing Chen1 Leilei Wu2 Boyue Pang1 Chunxia Su1*
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1 Department of Comprehensive Oncology Center, Shanghai Pulmonary Hospital & Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China
2 Department of Radiation Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
OR 2026, 2(1), 026020002 https://doi.org/10.36922/OR026020002
Received: 10 January 2026 | Revised: 13 February 2026 | Accepted: 24 February 2026 | Published online: 9 March 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Abstract

Intratumoral heterogeneity, alongside the dynamic evolution of cancer cells, continues to pose principal obstacles to efficacious cancer therapies. Although patient-derived organoids (PDOs) represent the gold standard for recapitulating patient-specific histopathology, their full utility emerges only through integration with high-resolution molecular profiling. This review synthesizes recent progress in combining PDOs with multi-omics approaches—including genomics, single-cell transcriptomics, and spatial omics—to elucidate the underpinnings of therapeutic resistance. We initially explore how organoid genomic profiling can monitor clonal dynamics and subclonal selection under therapeutic pressure. Next, we underscore the contributions of single-cell RNA sequencing in delineating transcriptional plasticity, detecting infrequent drug-tolerant persister populations, and charting nongenetic adaptive pathways. Of particular importance, we address the nascent domain of spatial transcriptomics, which preserves the structural integrity of organoids to uncover how proximate cell–cell interactions and niche elements shield tumor cells from therapeutic insult. Through the fusion of these multifaceted datasets, we advance a novel paradigm that frames resistance not as a fixed binary state, but as a spatiotemporally evolving adaptive phenomenon. The review culminates in delineating the translational promise of this synergistic paradigm for devising combination regimens that concurrently address genetic aberrations and adaptive microenvironments.

Keywords
Patient-derived organoids
Multi-omics profiling
Therapeutic resistance
Spatiotemporal heterogeneity
Clonal evolution
Single-cell RNA sequencing
Funding
This work was supported by the Key Special Projects of the “14th Five-Year Plan” of the National Key R&D Program of China (2023YFC2508601, 2023YFC2508604, and 2023YFC2508605), the National Natural Science Foundation of China (grant numbers: 82072568, 82373320), the Shanghai Shenkang Hospital Development Center (grant number: SHDC12020110), the Shanghai Shenkang Development Research Physician Project (grant number: SHDC2022CRD048), and the Tongji University Medicine-X Interdisciplinary Research Initiative (2025–0554–ZD–08).
Conflict of interest
The authors declare that they have no competing interests.
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Organoid Research, Electronic ISSN: 3082-8503 Published by AccScience Publishing