# Antibody-drug conjugates with dual payloads for combating breast tumor heterogeneity and drug resistance

Source: https://onco.cc/key-papers/paper-yamazaki-nat-commun/  
OnCo record `paper-yamazaki-nat-commun` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Paper cited by one technology page and one idea page, indexed on Europe PMC as PubMed record 34112795 and published in Nature Communications; the citing pages link this DOI, which is how the record was matched.

## Summary

Breast tumors generally consist of a diverse population of cells with varying gene expression profiles. Breast tumor heterogeneity is a major factor contributing to drug resistance, recurrence, and metastasis after chemotherapy. Antibody-drug conjugates (ADCs) are emerging chemotherapeutic agents with striking clinical success, including T-DM1 for HER2-positive breast cancer. However, these ADCs often suffer from issues associated with intratumor heterogeneity. Here, we show that homogeneous ADCs containing two distinct payloads are a promising drug class for addressing this clinical challenge. Our conjugates show HER2-specific cell killing potency, desirable pharmacokinetic profiles, minimal inflammatory response, and marginal toxicity at therapeutic doses. Notably, a dual-drug ADC exerts greater treatment effect and survival benefit than does co-administration of two single-drug variants in xenograft mouse models representing intratumor HER2 heterogeneity and elevated drug resistance. Our findings highlight the therapeutic potential of the dual-drug ADC format for treating refractory breast cancer and perhaps other cancers.

Indexed on Europe PMC as PubMed record 34112795 (DOI 10.1038/s41467-021-23793-7). Matched by DOI alone: one technology page and one idea page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.

## Fields

- Kind: Key paper
- Last checked: 2026-09-22
- Tags: europepmc-ingest
- Journal: Nature Communications
- Year: 2021
- DOI: 10.1038/s41467-021-23793-7
- Authors: Yamazaki CM, Yamaguchi A, Anami Y, et al.
- What it means: One technology page and one idea page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
- Caveats: Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper.

## Sources

- Nat Commun 2021: https://doi.org/10.1038/s41467-021-23793-7
- PubMed: https://pubmed.ncbi.nlm.nih.gov/34112795/
- Europe PMC: https://europepmc.org/article/MED/34112795

## Connected records

- technologies: [Dual-payload ADC](https://onco.cc/technologies/dual-payload-adc/)
- ideas: [Dual-payload ADCs in first line to prevent resistance](https://onco.cc/ideas/idea-dual-payload-first/)
- journals: [Nature Communications](https://onco.cc/journals/nature-communications/)

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