Evidence map›Paper›PMID 40203476›Full record

ReviewDNA repair2025

Werner helicase as a therapeutic target in mismatch repair deficient colorectal cancer.

Suisui Hao, Zhaojin Liu, Heinz-Josef Lenz, Jian Yu, Lin Zhang

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in DNA repair, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. Article
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.

Suisui HaoDepartment of Medicine, Keck School of Medicine of University of Southern California (USC), Los Angeles, CA 90033, USA; Norris Comprehensive Cancer Center, Keck School of Medicine of USC, Los Angeles, CA 90033, USA.
Zhaojin LiuDepartment of Medicine, Keck School of Medicine of University of Southern California (USC), Los Angeles, CA 90033, USA; Norris Comprehensive Cancer Center, Keck School of Medicine of USC, Los Angeles, CA 90033, USA.
Heinz-Josef LenzDepartment of Medicine, Keck School of Medicine of University of Southern California (USC), Los Angeles, CA 90033, USA; Norris Comprehensive Cancer Center, Keck School of Medicine of USC, Los Angeles, CA 90033, USA.
Jian YuDepartment of Medicine, Keck School of Medicine of University of Southern California (USC), Los Angeles, CA 90033, USA; Norris Comprehensive Cancer Center, Keck School of Medicine of USC, Los Angeles, CA 90033, USA.
Lin ZhangDepartment of Medicine, Keck School of Medicine of University of Southern California (USC), Los Angeles, CA 90033, USA; Norris Comprehensive Cancer Center, Keck School of Medicine of USC, Los Angeles, CA 90033, USA. Electronic address: lzhang24@usc.edu.

Funding

USC/NORRIS COMPREHENSIVE CANCER CENTER (CORE) SUPPORTP30CA014089 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Fumito Ito · 1985 to 2026
$181.4M
STING-dependent Intestinal Regeneration upon Radiation InjuryR01CA260900 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI YU, JIAN · 2022 to 2025
$2.5M
Targeting defective necroptosis in colorectal cancerR01CA247231 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ZHANG, LIN · 2020 to 2024
$2.3M
Role of necroptosis in colorectal cancer therapyR01CA236271 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ZHANG, LIN · 2019 to 2023
$2.2M
BET degraders for improving colorectal cancer therapyR01CA248112 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ZHANG, LIN · 2021 to 2025
$2.1M
NCI NIH HHS P30 CA014089NCI NIH HHS R01 CA236271NCI NIH HHS R01 CA247231NCI NIH HHS R01 CA248112NCI NIH HHS R01 CA260900
6 · The paper itself

Abstract

Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths in the United States. A key driver of CRC development is microsatellite instability (MSI), which is caused by DNA mismatch repair deficiency and characterized by hypermutability of short-tandem repeat sequences. A significant portion of MSI CRCs do not respond to checkpoint immunotherapy treatments, highlighting an unmet need for improved therapies. Recent studies have revealed that MSI cancer cells require Werner (WRN), a RecQ family DNA helicase, for survival. Inhibiting WRN has emerged as a promising approach for targeting MSI CRCs that are insensitive to standard therapies. Several highly potent small-molecule WRN inhibitors have been developed and exhibited striking in vitro and in vivo activities against MSI cancers. Two of these WRN inhibitors, HRO761 and VVD-133214, have recently entered clinical trials. In this review, we summarize recent studies on WRN as a synthetic lethal target in MSI CRC and the development of WRN inhibitors as a new class of anticancer agents.

Indexed as

Antineoplastic AgentsColorectal NeoplasmsDNA Mismatch RepairEnzyme InhibitorsWerner Syndrome HelicaseAnimalsHumansMicrosatellite InstabilityMolecular Targeted TherapyAntineoplastic AgentsEnzyme InhibitorsWerner Syndrome HelicaseWRN protein, humanColorectal cancerDrug developmentImmunotherapyMicrosatellite instabilityMismatch repairTherapeutic resistanceWerner helicase

Identifiers

PMID40203476
PMCPMC12086038

What OpenQuestion holds

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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.