Evidence map›Paper›PMID 34358100›Full record

ReviewPharmaceuticals (Basel, Switzerland)2021

Impact of Endocytosis Mechanisms for the Receptors Targeted by the Currently Approved Antibody-Drug Conjugates (ADCs)-A Necessity for Future ADC Research and Development.

Manar Hammood, Andrew W Craig, Jeffrey V Leyton

Registry-linked trialOpen access · goldAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Pharmaceuticals (Basel, Switzerland), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07610616 (Study on the Mechanism of ADC Drug Evaluation Based on Immune Co-culture of Lung Cancer Organoids), which is not on this map. Cited by 72 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed, 3 pooled it
6.1field-weighted citation impact, top 3% 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.

NCT07610616 recruitingnot on this mapstarted 2025, after this paper: background citation

Study on the Mechanism of ADC Drug Evaluation Based on Immune Co-culture of Lung Cancer Organoids

TypeobservationalSponsorGuangzhou Institute of Respiratory DiseaseRan2025 to 2027Enrolled10ConditionsHER2 Positive OR TROP2 Positive Non-Small Cell Lung CancerArmsAntibody-drug conjugate (ADC) combination therapy
3 · Its place in the literature

Who cites it

72 citing papers in PubMed, 3 syntheses or guidelines pooled it, 94 citations in OpenAlex.

  1. [Clinical Progress and Prospects of Antibody-drug Conjugates in Advanced NSCLC].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2025
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  18. Predictive Biomarkers of Antibody-Drug Conjugate Efficacy for Solid Tumors: Current Challenges and the Potential Role of Quantitative Proteomics.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
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12 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

3 authors at 2 institutions in 1 country.

Manar HammoodDepartément de Medécine Nucléaire et Radiobiologie, Faculté de Medécine et des Sciences de la Santé, Centre Hospitalier Universitaire de Sherbrooke (CHUS), Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada.
Andrew W CraigDepartment of Biomedical and Molecular Sciences, Queen's University, Kingston, ON K7L 3N6, Canada.
Jeffrey V LeytonDepartément de Medécine Nucléaire et Radiobiologie, Faculté de Medécine et des Sciences de la Santé, Centre Hospitalier Universitaire de Sherbrooke (CHUS), Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada.ORCID 0000-0001-6870-3819
Université de Sherbrooke · CAQueen's University · CA

Funding

CIHR 201610PJT-378389-PJT-CFDA-190713
6 · The paper itself

Abstract

Biologically-based therapies increasingly rely on the endocytic cycle of internalization and exocytosis of target receptors for cancer therapies. However, receptor trafficking pathways (endosomal sorting (recycling, lysosome localization) and lateral membrane movement) are often dysfunctional in cancer. Antibody-drug conjugates (ADCs) have revitalized the concept of targeted chemotherapy by coupling inhibitory antibodies to cytotoxic payloads. Significant advances in ADC technology and format, and target biology have hastened the FDA approval of nine ADCs (four since 2019). Although the links between aberrant endocytic machinery and cancer are emerging, the impact of dysregulated internalization processes of ADC targets and response rates or resistance have not been well studied. This is despite the reliance on ADC uptake and trafficking to lysosomes for linker cleavage and payload release. In this review, we describe what is known about all the target antigens for the currently approved ADCs. Specifically, internalization efficiency and relevant intracellular sorting activities are described for each receptor under normal processes, and when complexed to an ADC. In addition, we discuss aberrant endocytic processes that have been directly linked to preclinical ADC resistance mechanisms. The implications of endocytosis in regard to therapeutic effectiveness in the clinic are also described. Unexpectedly, information on endocytosis is scarce (absent for two receptors). Moreover, much of what is known about endocytosis is not in the context of receptor-ADC/antibody complexes. This review provides a deeper understanding of the pertinent principles of receptor endocytosis for the currently approved ADCs.

Indexed as

antibody-drug conjugateBCMACD22CD30CD33CD79bendocytosisendophilin A2HER2nectin-4trop2

Identifiers

PMID34358100
PMCPMC8308841
OpenAlexW3182715110

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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.