ArticleBJC reports2024
High-dose short-term osimertinib treatment is effective in patient-derived metastatic colorectal cancer organoids.
Article in BJC reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
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The trial behind it
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Who cites it
5 citing papers in PubMed.
- SUNRISE-CRC: a randomized phase II study of high-dose intermittent sunitinib versus trifluridine/tipiracil in metastatic colorectal carcinoma.The oncologist · 2025Trial
- Article
- The Phenotypical and Functional Effect of PGE2 on Human Macrophages.European journal of immunology · 2025Article
- Exploring research frontiers and emerging trends of tyrosine kinase inhibitors in the treatment of colorectal cancer.BMC cancer · 2025Article
- EP2 and EP4 blockade prevents tumor-induced suppressive features in human monocytic myeloid-derived suppressor cells.Frontiers in immunology · 2024Article
Corrections and comments
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMost tyrosine kinase inhibitors (TKIs) have failed in clinical trials for metastatic colorectal cancer (mCRC). To leverage the additional lower-affinity targets that most TKIs have, high-dose regimens that trigger efficacy are explored. Here, we studied unprecedented drug exposure-response relationships in vitro using mCRC patient-derived tumour organoids (PDTOs).
methodsWe investigated the cytotoxic anti-tumour effect of high-dose, short-term (HDST) TKI treatment on 5 PDTOs. Sunitinib, cediranib and osimertinib were selected based on favourable physicochemical and pharmacokinetic properties. Intra-tumoroid TKI concentrations were measured using a clinically validated LC/MS-MS method. Cell death was determined using an enzyme activity assay, immunofluorescent staining and western blotting.
resultsMost PDTOs tested were sensitive to sunitinib and cediranib, but all to osimertinib. Furthermore, HDST osimertinib treatment effectively blocks organoid growth. This treatment led to markedly elevated intra-tumoroid TKI concentrations, which correlated with PDTO sensitivity. Mechanistically, HDST osimertinib treatment induced apoptosis in treated PDTOs.
conclusionOur work provides a better understanding of TKI exposure vs response and can be used to determine patient-specific sensitivity. Additionally, these results may guide both mechanistic elucidation in organotypic translational models and the translation of target drug exposure to clinical dosing strategies. Moreover, HDST osimertinib treatment warrants clinical exploration for mCRC.
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