Evidence map›Paper›PMID 39745621›Full record

ReviewFrontiers of medicine2025

Canonical and noncanonical NOTCH signaling in the nongenetic resistance of cancer: distinct and concerted control.

Xianzhe Huang, Wenwei Chen, Yanyan Wang, Dmytro Shytikov, Yanwen Wang, Wangyi Zhu, Ruyi Chen, Yuwei He, Yanjia Yang, Wei Guo

Abstract readReview
PubMed Publisher
In one paragraph

Review in Frontiers of medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Article
  5. 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

10 authors.

Xianzhe Huang *Zhejiang University-University of Edinburgh Institute, School of Medicine, Zhejiang University, Jiaxing, 314400, China.
Wenwei Chen *Zhejiang University-University of Edinburgh Institute, School of Medicine, Zhejiang University, Jiaxing, 314400, China.
Yanyan Wang *Zhejiang University-University of Edinburgh Institute, School of Medicine, Zhejiang University, Jiaxing, 314400, China.
Dmytro ShytikovZhejiang University-University of Edinburgh Institute, School of Medicine, Zhejiang University, Jiaxing, 314400, China.
Yanwen WangZhejiang University-University of Edinburgh Institute, School of Medicine, Zhejiang University, Jiaxing, 314400, China.
Wangyi ZhuZhejiang University-University of Edinburgh Institute, School of Medicine, Zhejiang University, Jiaxing, 314400, China.
Ruyi ChenZhejiang University-University of Edinburgh Institute, School of Medicine, Zhejiang University, Jiaxing, 314400, China.
Yuwei HeZhejiang University-University of Edinburgh Institute, School of Medicine, Zhejiang University, Jiaxing, 314400, China.
Yanjia YangZhejiang University-University of Edinburgh Institute, School of Medicine, Zhejiang University, Jiaxing, 314400, China.
Wei GuoZhejiang University-University of Edinburgh Institute, School of Medicine, Zhejiang University, Jiaxing, 314400, China. weiguo@intl.zju.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Therapeutic resistance in cancer is responsible for numerous cancer deaths in clinical practice. While target mutations are well recognized as the basis of genetic resistance to targeted therapy, nontarget mutation resistance (or nongenetic resistance) remains poorly characterized. Despite its complex and unintegrated mechanisms in the literature, nongenetic resistance is considered from our perspective to be a collective response of innate or acquired resistant subpopulations in heterogeneous tumors to therapy. These subpopulations, e.g., cancer stem-like cells, cancer cells with epithelial-to-mesenchymal transition, and drug-tolerant persisters, are protected by their resistance traits at cellular and molecular levels. This review summarizes recent advances in the research on resistant populations and their resistance traits. NOTCH signaling, as a central regulator of nongenetic resistance, is discussed with a special focus on its canonical maintenance of resistant cancer cells and noncanonical regulation of their resistance traits. This novel view of canonical and noncanonical NOTCH signaling pathways is translated into our proposal of reshaping therapeutic strategies targeting NOTCH signaling in resistant cancer cells. We hope that this review will lead researchers to study the canonical and noncanonical arms of NOTCH signaling as an integrated resistant mechanism, thus promoting the development of innovative therapeutic strategies.

Indexed as

Disease ResistanceNeoplasmsReceptors, NotchDrug Resistance, NeoplasmHumansMolecular Targeted TherapySignal TransductionReceptors, Notchcancer stemlike cellscanonical NOTCH signalingdrug-tolerant persistersepithelial-to-mesenchymal transitionnoncanonical NOTCH signalingnongenetic resistance of cancerNOTCH inhibitors

Identifiers

PMID39745621

What OpenQuestion holds

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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.