Molecular Determinants of Response and Rational Drug Combinations for Antibody-Drug Conjugates (ADCs) with Topoisomerase I (TOP1) Inhibitor Payloads.

Yves Pommier

Abstract readReview

In one paragraph

Review in Journal of molecular biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it

0cells of the map it votes in

0citing papers in PubMed

–field-weighted citation impact

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

1 author.

Yves PommierLaboratory of Molecular Pharmacology and Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, United States. Electronic address: pommier@nih.gov.

Funding

DNA Repair, Cell Cycle Checkpoints and Apoptosis as Targets for Anticancer DrugsZIABC006150 · DIVISION OF BASIC SCIENCES - NCI · 2025 to 2025

$1.0M

PROTEIN-ASSOCIATED DNA BREAKS AS INDICATOR OF TOPOISOMERASE INHIBITIONZ01BC006150 · BASIC SCIENCES · 1996 to 2005

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DNA TOPOISOMERASES AS TARGET OF ACTION OF ANTICANCER DRUGSZ01BC006161 · BASIC SCIENCES · 1996 to 2005

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Intramural NIH HHS Z01 BC006150Intramural NIH HHS Z01 BC006161Intramural NIH HHS ZIA BC006150

6 · The paper itself

Abstract

Here we describe the different TOP1 poisons used a "payload" for tumor-targeted anticancer therapies in comparison with the widely used first generation TOP1 poisons: Topotecan, Irinotecan and Belotecan. We review the determinants of response to tumor-targeted TOP1 poison inhibitors (TTTis) as candidate companion diagnostic (Dx) biomarkers for precision medicine and patient selection, such as high expression of surface epitopes for ADCs (Antibody Drug Conjugates), high tumor proliferation (Ki67), Schlafen 11 (SLFN11) expression, homologous recombination deficiencies (HRD/BRCAness) and expression of drug efflux transporters such as (BCRP (MXR) encoded by ABCG2. We also summarize the mechanistic rationale for combining TTTis with small molecule inhibitors of poly(ADPribose) polymerase (PARP), ATR (Ataxia Telangiectasia and Rad3-related), CHK1 (Checkpoint Kinase 1) and ATM (Ataxia Telangiectasia Mutated).

Indexed as

DNA Topoisomerases, Type IImmunoconjugatesNeoplasmsTopoisomerase I InhibitorsHumansDNA Topoisomerases, Type IImmunoconjugatesTOP1 protein, humanTopoisomerase I Inhibitorsbiomarkershomologous recombinationpoly(ADP)riboseSchlafen 11topoisomerase

Identifiers

PMID42092629

DOI10.1016/j.jmb.2026.169841

PMCPMC13231283

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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 Socratic graph.