Evidence map›Paper›PMID 34112795›Full record

ArticleNature communications2021

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

Chisato M Yamazaki, Aiko Yamaguchi, Yasuaki Anami, Wei Xiong, Yoshihiro Otani, Jangsoon Lee, Naoto T Ueno, Ningyan Zhang, Zhiqiang An, Kyoji Tsuchikama

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 169 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
169citing papers in PubMed, 2 pooled it
15.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

169 citing papers in PubMed, 2 syntheses or guidelines pooled it, 269 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Review
  5. Article
  6. Antibody-drug conjugate engineering: from design to efficacy and safety.Signal transduction and targeted therapy · 2026
    Review
  7. Article
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  16. Pyridine-containing antitumor agents: structure-oriented medicinal chemistry, structure-activity relationships, and ADMET liabilities.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026
    Review
  17. Dynamic monitoring of antibody drug conjugates targeting TROP2 or HER2 in breast cancer using circulating tumor cells.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  18. Article
  19. Article
  20. Article

109 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 1 country.

Chisato M Yamazaki *Texas Therapeutics Institute, The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX, USA.ORCID 0000-0002-0785-7352
Aiko Yamaguchi *Texas Therapeutics Institute, The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX, USA.ORCID 0000-0002-7631-3164
Yasuaki AnamiTexas Therapeutics Institute, The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX, USA.ORCID 0000-0001-5136-7708
Wei XiongTexas Therapeutics Institute, The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Yoshihiro OtaniDepartment of Neurosurgery, The University of Texas Health Science Center at Houston, Houston, TX, USA.ORCID 0000-0002-1615-5125
Jangsoon LeeSection of Translational Breast Cancer Research, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Naoto T UenoSection of Translational Breast Cancer Research, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID 0000-0002-0166-7275
Ningyan ZhangTexas Therapeutics Institute, The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX, USA.ORCID 0000-0002-4348-2180
Zhiqiang AnTexas Therapeutics Institute, The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX, USA.ORCID 0000-0001-9309-2335
Kyoji TsuchikamaTexas Therapeutics Institute, The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX, USA. Kyoji.Tsuchikama@uth.tmc.edu.ORCID 0000-0002-2359-0408
Brown Foundation · USThe University of Texas MD Anderson Cancer Center · USThe University of Texas Health Science Center at Houston · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
NCI NIH HHS P30 CA016672
6 · The paper itself

Abstract

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 as

AnimalsAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsCell Line, TumorErb-b2 Receptor Tyrosine KinasesFemaleHumansImmunoconjugatesImmunohistochemistryInflammationMiceOligopeptidesTrastuzumabXenograft Model Antitumor AssaysAntineoplastic AgentsERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesImmunoconjugatesmonomethyl auristatin Emonomethylauristatin FOligopeptidesTrastuzumab

Identifiers

PMID34112795
PMCPMC8192907
OpenAlexW3167756601

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.