Evidence map›Paper›PMID 40300769›Full record

ArticleACS chemical biology2025

Exploring the Potential of Homologous Recombination Protein PALB2 in Synthetic Lethal Combinations.

Xinyan Lu, Basilius Sauter, Aramis Keller, Saule Zhanybekova, Dennis Gillingham

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in ACS chemical biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
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

5 authors.

Xinyan LuDepartment of Chemistry, University of Basel, 4056 Basel, Switzerland.
Basilius SauterDepartment of Chemistry, University of Basel, 4056 Basel, Switzerland.ORCID 0000-0002-3199-3397
Aramis KellerDepartment of Chemistry, University of Basel, 4056 Basel, Switzerland.
Saule ZhanybekovaDepartment of Chemistry, University of Basel, 4056 Basel, Switzerland.
Dennis GillinghamDepartment of Chemistry, University of Basel, 4056 Basel, Switzerland.ORCID 0000-0002-3672-8699

Funding

Swiss National Science Foundation CRSII5_186230
6 · The paper itself

Abstract

Cells with defective homologous recombination (HR) are highly sensitive to poly(ADP-ribose) polymerase (PARP) inhibition. Current therapeutic approaches leverage this vulnerability by using PARP inhibitors in cells with genetically compromised HR. However, if HR factors in cancer cells could be inhibited or degraded pharmacologically, it might reveal other opportunities for synergistic combinations. In this study, we developed a model system that recapitulates PARP/HR synthetic lethality by integrating a small-molecule responsive zinc-finger degron into the HR factor Partner and Localizer of BRCA2 (PALB2). We further tested a series of peptide ligands for PALB2 based on its natural binding partners, which led to the discovery of a high affinity peptide that will support future work on PALB2 and HR. Together, our findings validate PALB2 as a promising drug target and provide the tools and starting points for developing molecules with therapeutic applications.

Indexed as

Fanconi Anemia Complementation Group N ProteinHomologous RecombinationSynthetic Lethal MutationsBRCA2 ProteinCell Line, TumorHumansPeptidesPoly(ADP-ribose) Polymerase InhibitorsZinc FingersBRCA2 ProteinFanconi Anemia Complementation Group N ProteinPALB2 protein, humanPeptidesPoly(ADP-ribose) Polymerase Inhibitors

Identifiers

PMID40300769
PMCPMC12090178

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Registered trials

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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 OpenQuestion graph.