# Linked human organ chips to predict side effects before people are dosed

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

## TL;DR

Damage to the lungs, heart or liver is a common reason cancer drugs fail. Connected chips of human tissue may spot this earlier than animal tests.

## Summary

Interstitial lung disease with ADCs, cardiotoxicity with HER2 agents and hepatotoxicity with several classes are poorly predicted by rodents. Coupled microphysiological systems with human lung, heart, liver and kidney compartments and shared circulation can measure organ-specific injury from a candidate at clinically relevant exposures. US legislation now allows non-animal methods to support investigational new drug applications, giving a regulatory route.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Hypothesis: A multi-organ chip panel correctly identifies the organ of clinical dose-limiting toxicity for the majority of a retrospective set of ADCs with known human toxicity profiles.
- Rationale: ADC toxicity is frequently payload- and off-target-driven in human-specific ways; the chips are human by construction, and the retrospective validation set already exists.
- Proposed test: Blinded retrospective study across 15 ADCs and kinase inhibitors with known clinical toxicity, scoring organ prediction accuracy against animal study predictions.
- 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/)
- terms: [Interstitial lung disease (ILD) / pneumonitis](https://onco.cc/terms/ild/), [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/), [Toxicity and quality of life are undervalued](https://onco.cc/bottlenecks/b-toxicity-qol/)
- key papers: [Estimation of clinical trial success rates and related parameters](https://onco.cc/key-papers/paper-wong-biostatistics/)
- roadmaps: [Drug discovery roadmap: screening in mice → maps of dependency → designing in silico](https://onco.cc/roadmaps/drug-discovery-roadmap/)

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