# Tumour-on-a-chip with blood flow to test whether big drugs actually get in

Source: https://onco.cc/ideas/idea-bio1-tumour-on-chip-penetration/  
OnCo record `idea-bio1-tumour-on-chip-penetration` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Large drugs such as antibody-drug conjugates must cross vessel walls and travel through dense tissue. A chip with flowing channels and human tissue can measure how far they get.

## Summary

Microphysiological systems with perfusable endothelial channels, stromal fibroblasts and tumour spheroids reproduce interstitial pressure, matrix density and convective transport, the variables that determine ADC, radioligand and nanoparticle penetration. Standard flat cultures and mouse models cannot measure human tissue penetration directly, and penetration is a leading cause of clinical underperformance for large modalities.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Hypothesis: Chip-measured penetration depth and payload delivery rank a set of ADCs in the same order as their observed clinical activity in matched indications.
- Rationale: Payload delivered per gram of tumour is a mechanistic determinant of ADC efficacy; the binding-site barrier and stromal exclusion are well described but rarely measured before clinical trials.
- Proposed test: Benchmark five clinically characterised ADCs with divergent outcomes on a standardised chip and correlate penetration metrics with reported response rates.
- Maturity: preclinical-evidence
- Actor: engineering

## Sources

- Bottleneck evidence (Lab models that fail to predict what happens in patients): Wong, Siah & Lo, Estimation of clinical trial success rates (Biostatistics 2019): https://doi.org/10.1093/biostatistics/kxx069

## Connected records

- technologies: [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/), [Patient-derived organoids](https://onco.cc/technologies/organoids/), [Radioligand therapy (beta emitters)](https://onco.cc/technologies/radioligand-therapy/)
- drugs: [Sacituzumab govitecan](https://onco.cc/drugs/sacituzumab-govitecan/), [Trastuzumab deruxtecan](https://onco.cc/drugs/trastuzumab-deruxtecan/)
- terms: [Bystander effect (ADC)](https://onco.cc/terms/bystander-effect/), [Payload (ADC)](https://onco.cc/terms/payload/)
- bottlenecks: [Lab models that fail to predict what happens in patients](https://onco.cc/bottlenecks/b-preclinical-models/)
- key papers: [Estimation of clinical trial success rates and related parameters](https://onco.cc/key-papers/paper-wong-biostatistics/)

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