---
title: "Boolean-network simplification identifies mechanisms of chemotherapy resistance in non‑small‑cell"
id: "pubmed-42743272"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42743272"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42743272/"
doi: "10.1371/journal.pone.0357764"
published_at: "2026-09-15T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Boolean-network simplification identifies mechanisms of chemotherapy resistance in non‑small‑cell
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42743272
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42743272/)
- **DOI:** [10.1371/journal.pone.0357764](https://doi.org/10.1371%2Fjournal.pone.0357764)
- **Published At:** 2026-09-15T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- The study applies Boolean-network reduction to a published 31-node model of chemotherapy resistance in **non‑small‑cell lung cancer** to derive a compact core network that preserves key dynamics. - A biologically guided sequence of reductions (31 → 29 → 14 → 9 nodes) produced a **9‑node core** that exactly reproduces the original model's attractor landscape while reducing computational complexity. - The reduced network decreases the state space by **four orders of magnitude**, enabling faster exploration of control points and computational analyses. - The authors performed extensive synchronous and asynchronous simulations to validate dynamical equivalence between the original and reduced models. - A Boolean rule‑fitting algorithm was applied to the reduced model; it removes spurious limit cycles and refines rules so attractors match clinically relevant steady states. - The reduced model conserves three clinically relevant steady states and their basins of attraction; simulated resistance frequencies align closely with frequencies reported in clinical studies. - The streamlined network is presented as an accessible scaffold for mechanistic studies, rule fitting, and candidate therapeutic target identification in chemotherapy resistance, notably for **cisplatin** and **pemetrexed** resistance. - The paper reports that the approach facilitates rapid exploration of critical control points but does not detail experimental validation beyond computational simulations in the abstract.
## Clinical Analysis & Structured Key Points
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Affiliations Expand ### Affiliations * 1 Facultad de Ingenieria y Ciencias, Univesidad Adolfo Ibañez, Santiago, Chile. * 2 Laboratoire d'Informatique et Systèmes, Centre National de la Recherche Scientifique, Aix-Marseille Univesité, Marseille, France. * 3 Millennium Nucleus for Social Data Science (SODAS), Santiago, Chile. * PMID: **42743272** * DOI: [ 10.1371/journal.pone.0357764 ](https://doi.org/10.1371/journal.pone.0357764) Item in Clipboard # Boolean-network simplification and rule fitting to unravel chemotherapy resistance in non-small cell lung cancer Alonso Espinoza et al. PLoS One. 2026. Show details Display options Display options Format Abstract PubMed PMID PLoS One Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22PLoS+One%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22PLoS+One%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42743272/) . 2026 Sep 15;21(9):e0357764. doi: 10.1371/journal.pone.0357764. eCollection 2026. ### Authors [Alonso Espinoza](https://pubmed.ncbi.nlm.nih.gov/?term=Espinoza+A&cauthor_id=42743272)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42743272/#short-view-affiliation-1 "Facultad de Ingenieria y Ciencias, Univesidad Adolfo Ibañez, Santiago, Chile.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42743272/#short-view-affiliation-2 "Laboratoire d'Informatique et Systèmes, Centre National de la Recherche Scientifique, Aix-Marseille Univesité, Marseille, France."), [Eric Goles](https://pubmed.ncbi.nlm.nih.gov/?term=Goles+E&cauthor_id=42743272)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42743272/#short-view-affiliation-1 "Facultad de Ingenieria y Ciencias, Univesidad Adolfo Ibañez, Santiago, Chile.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42743272/#short-view-affiliation-3 "Millennium Nucleus for Social Data Science \(SODAS\), Santiago, Chile."), [Marco Montalva-Medel](https://pubmed.ncbi.nlm.nih.gov/?term=Montalva-Medel+M&cauthor_id=42743272)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42743272/#short-view-affiliation-1 "Facultad de Ingenieria y Ciencias, Univesidad Adolfo Ibañez, Santiago, Chile.") ### Affiliations * 1 Facultad de Ingenieria y Ciencias, Univesidad Adolfo Ibañez, Santiago, Chile. * 2 Laboratoire d'Informatique et Systèmes, Centre National de la Recherche Scientifique, Aix-Marseille Univesité, Marseille, France. * 3 Millennium Nucleus for Social Data Science (SODAS), Santiago, Chile. * PMID: **42743272** * DOI: [ 10.1371/journal.pone.0357764 ](https://doi.org/10.1371/journal.pone.0357764) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## Abstract Boolean networks are powerful frameworks for capturing the logic of gene-regulatory circuits, yet their combinatorial explosion hampers exhaustive analyses. Here, we present a systematic reduction of a published 31-node Boolean model that describes cisplatin- and pemetrexed-resistance in non-small-cell lung cancer to a compact 9-node core that exactly reproduces the original attractor landscape. Through a sequence of biologically guided reductions (31→29→14→9 nodes), the streamlined network shrinks the state space by four orders of magnitude, enabling rapid exploration of critical control points, rules fitting, and candidate therapeutic targets. Extensive synchronous and asynchronous simulations, combined with a Boolean rule-fitting algorithm that removes spurious limit cycles, confirm that the three clinically relevant steady states and their basins of attraction are conserved and reflect resistance frequencies close to those reported in clinical studies. The reduced model provides an accessible scaffold for future mechanistic and drug-discovery studies. Copyright: © 2026 Espinoza et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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