Evidence map›Paper›PMID 42014800›Full record

ArticleScientific reports2026

Increased vulnerability of colorectal cancer models with high alkylation damage to NTHL1 inactivation.

Hyeoncheol Kim, Jules Cazaubiel, Tung-Lin Chiang, Dimitrios Stylianakis, Samantha Fitzgerald, Pushpamali De Silva, Carino Gurjao, Marios Giannakis

Abstract read
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In one paragraph

Article in Scientific reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
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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

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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

8 authors.

Hyeoncheol KimDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Jules CazaubielDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Tung-Lin ChiangDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Dimitrios StylianakisDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Samantha FitzgeraldDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Pushpamali De SilvaDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Carino GurjaoDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Marios GiannakisDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Marios_giannakis@dfci.harvard.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The mutational signature of alkylating damage is highly similar to the one associated with inactivation of NTHL1, a gene involved in Base Excision Repair. We hypothesized that colorectal cancers (CRCs) with high alkylation damage, could be selectively vulnerable to NTHL1 deletion. We found that CRC cells and patient-derived organoids with high alkylation damage, coupled with NTHL1 inactivation, are less viable and exhibit reduced cellular proliferation due to heightened DNA damage repair response and G2/S cell cycle arrest. CHK1 inhibition in this subset of tumors led to enhanced apoptosis. Notably, CRCs with low alkylation, following treatment with alkylating agents, also exhibit vulnerability to NTHL1 deletion and increased sensitivity to CHK1 inhibition. Our study thus demonstrates that the combination of alkylation damage and NTHL1 inactivation leads to synthetic sickness in CRC, further sensitization to CHK1 inhibition, and reveals potential therapeutic vulnerabilities in CRC.

Indexed as

Colorectal NeoplasmsDNA DamageAlkylationAnimalsApoptosisCell Line, TumorCell ProliferationCheckpoint Kinase 1DNA RepairExcision RepairHumansCheckpoint Kinase 1CHEK1 protein, humanBase excision repair (BER)Colorectal cancerDNA alkylationDNA damageSynthetic lethality

Identifiers

PMID42014800
PMCPMC13269758

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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.