{
  "abstract": "Treatment resistance is usually attributed to genetic or adaptive changes within tumor cells. Here, we propose that, in some tumors, resistance also depends on specific interactions between malignant and non-malignant cells. We define relational resistance as a resistant phenotype that requires the functional organization of particular intercellular relationships. This concept is narrower than microenvironment-mediated resistance: the presence of stromal, immune, or vascular cells is not sufficient to establish relational resistance; a defined interaction must contribute functionally to treatment failure. We organize evidence along a five-step sequence: predicted edge, spatial support, functional edge, relational dependency, and therapeutic vulnerability. Genitourinary cancers illustrate different positions along this sequence: bladder cancer provides a predicted CD6–ALCAM edge with independent clinical association but without targeted perturbation; prostate cancer provides myeloid circuits with preclinical causal support and phase 1 proof-of-concept targetability; and renal cell carcinoma provides spatially organized multicellular programs with functional and preclinical perturbation support. We further propose relational memory as the hypothesis that a treatment-induced or treatment-selected interaction persists after therapy and influences response to a subsequent treatment. The framework therefore shifts the therapeutic question from which resistant cells are present to which relationships are required for resistance to persist.",
  "abstract_shown": true,
  "affiliations": [
    "University Hospital, Federal University of Pelotas - HUBrasil, Pelotas, Brazil",
    "Postgraduate Program in Biotechnology, Center for Technological Development, Federal University of Pelotas, Pelotas, Brazil"
  ],
  "article_type": "brief report",
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Daniele Silva Lacerda"
    },
    {
      "affs": [
        0
      ],
      "name": "Rosiane Batista Mastelari"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Tiago Veiras Collares"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2zb5gg7cyf51a.bib",
  "cited_by": 0,
  "doi": "10.3389/fonc.2026.1974982",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13696230/",
  "id": "2zb5gg7cyf51a",
  "issns": [
    "2234-943X"
  ],
  "landing_url": "https://doi.org/10.3389/fonc.2026.1974982",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Perspective"
    ],
    [
      "openalex",
      "2740|Prostate Cancer Treatment and Research"
    ]
  ],
  "openalex": "W7221456692",
  "pdf_url": "https://europepmc.org/articles/PMC13696230?pdf=render",
  "pmcid": "PMC13696230",
  "pmid": "42935737",
  "published": "2026-10-12",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/2zb5gg7cyf51a.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:37Z",
      "native_id": "PMC13696230",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fonc.2026.1974982"
    },
    {
      "first_seen": "2026-10-30T12:20:13Z",
      "native_id": "10.3389/fonc.2026.1974982",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fonc.2026.1974982/full"
    },
    {
      "first_seen": "2026-10-30T12:22:12Z",
      "native_id": "MED:42935737",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42935737"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "issn:2234-943X",
      "subfield": "oncology"
    }
  ],
  "title": "Resistance in the edges: a relational framework for treatment resistance in genitourinary cancers",
  "title_text": "Resistance in the edges: a relational framework for treatment resistance in genitourinary cancers",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:33:36Z",
  "url": "https://research.draconitic.com/paper/2zb5gg7cyf51a",
  "venue": "Frontiers in Oncology",
  "versions": []
}