{
  "abstract": "Protein phosphatase 2A (PP2A) is a multifunctional serine/threonine phosphatase that regulates cell-cycle progression, oncogenic signaling, neuronal development, synaptic homeostasis, and protein proteostasis. Its dysregulation contributes to cancer, whereas impaired PP2A activity in the nervous system is linked to neurodevelopmental disorders and neurodegenerative proteinopathies, including tau and α-synuclein pathology. These divergent roles create both opportunities and safety challenges for PP2A-directed therapies. This review examines PP2A as a modular holoenzyme system whose subunit composition determines substrate specificity and context-dependent biological effects. We discuss PP2A dysfunction in cancer, including genetic and regulatory alterations affecting PP2A subunits, assembly, and endogenous inhibitors, and compare therapeutic PP2A activation with transient inhibition. The latter approach is exemplified by LB100, which sensitizes treatment-stressed tumor cells to chemotherapy, radiotherapy, or immunotherapy by disrupting checkpoint adaptation and stress recovery. We further evaluate the neurological implications of systemic phosphatase inhibition, LB100 conversion to the active metabolite endothall, clinical safety and pharmacokinetic data, and the limited brain-tumor penetration of intact LB100. We propose that the clinical utility of PP2A inhibition depends on defining a therapeutic corridor that integrates dosing schedule, parent-drug and metabolite exposure, tumor target engagement, biomarker-informed patient selection, and preservation of PP2A-dependent homeostasis in normal tissues, particularly the nervous system.",
  "abstract_shown": true,
  "affiliations": [
    "Advitam Laboratory, Belgrade, Serbia.",
    "Institute of Cytology RAS, St. Petersburg, Russia.",
    "The Laboratory of Bio- and Chemoinformatics, School of Computer Science, Physics and Technology, HSE University, St. Petersburg, Russia.",
    "Department of Neurobiology, Institute for Biological Research \"Siniša Stanković\" - National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia."
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Margarita Chigriai"
    },
    {
      "affs": [
        1
      ],
      "name": "Nina Kraskovskaya"
    },
    {
      "affs": [
        0
      ],
      "name": "Anastasia Bolshakova"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Natalia O Porozova"
    },
    {
      "affs": [
        2
      ],
      "name": "Yuri B Porozov"
    },
    {
      "affs": [
        3
      ],
      "name": "Milica Pešić"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/f4kympdr5fvjw.bib",
  "cited_by": 0,
  "doi": "10.3389/fcell.2026.1945801",
  "fulltext_url": "https://europepmc.org/articles/PMC13710974",
  "id": "f4kympdr5fvjw",
  "issns": [
    "2296-634X"
  ],
  "landing_url": "https://europepmc.org/article/MED/42947971",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Review"
    ],
    [
      "openalex",
      "1312|Protein Tyrosine Phosphatases"
    ]
  ],
  "openalex": "W7221687434",
  "pdf_url": "https://europepmc.org/articles/PMC13710974?pdf=render",
  "pmcid": "PMC13710974",
  "pmid": "42947971",
  "published": "2026-10-13",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/f4kympdr5fvjw.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:20:34Z",
      "native_id": "MED:42947971",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42947971"
    },
    {
      "first_seen": "2026-10-31T12:21:50Z",
      "native_id": "PMC13710974",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fcell.2026.1945801"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Protein Tyrosine Phosphatases",
      "subfield": "molecular-biology"
    }
  ],
  "title": "PP2A targeting: balancing anticancer potential and neurological risk.",
  "title_text": "PP2A targeting: balancing anticancer potential and neurological risk.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:21:50Z",
  "url": "https://research.draconitic.com/paper/f4kympdr5fvjw",
  "venue": "Frontiers in cell and developmental biology",
  "versions": []
}