{
  "abstract": "Purpose\n\nImmunotherapy with chemotherapy significantly improves progression-free survival in advanced endometrial cancer (EC), especially in microsatellite instability-high (MSI-H) cases. Despite this, for recurrent EC in the postimmunotherapy setting, new treatment options are urgently needed. The PI3K pathway is frequently altered in gynecologic cancers, including EC, representing a potential treatment target.Patients and methods\n\nIn a preplanned translational analysis of the MITO END-3, we retrospectively analyzed the genomic abnormalities of 107 patients with samples eligible for next-generation sequencing (NGS) analysis (FoundationOne CDx) with a focus on PIK3CA mutational status.Results\n\nIn our analysis, the four most frequently mutated genes were TP53, PIK3CA, ARID1A, and PTEN. PIK3CA mutations were detected in 51.4% (55/107 patients) of tissue samples. A total of 68 different PIK3CA mutations were observed, of which 64 were considered pathogenic and four were classified as variants of unknown significance, with the co-occurrence of two different pathogenic mutations in 2 patients. The most frequent PIK3CA mutations were found in the kinase domain, most commonly H1047R (11/68) and H1047Y (3/68), and in the helical domain, including E545K (4/68) and E542K (3/68). Notably, 24 different PIK3CA mutations out of 68 reported in MITO END-3 are considered predictive of response to PI3K inhibition with alpelisib according to current literature in breast cancer. Interestingly, PIK3CA mutations were observed in all The Cancer Genome Atlas categories.Conclusion\n\nIn this post hoc analysis from the MITO END-3 trial, we confirmed the high frequency of PIK3CA mutations in EC, establishing this tumor as an ideal candidate for testing of PI3K inhibitors in clinical trials.",
  "abstract_shown": true,
  "affiliations": [
    "Uro-Gynecological Medical Oncology, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, Naples, Italy.",
    "Bioinformatics Unit, Istituto Dermopatico dell'Immacolata IDI-IRCCS, Rome, Italy.",
    "Microenvironment Molecular Targets Unit, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, Naples, Italy.",
    "Unit of Medical Oncology and Cancer Prevention, Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy.",
    "Division of Gynecologic Oncology, Humanitas San Pio X, Milan, Italy.",
    "Department of Biomedical Sciences, Humanitas University, Milan, Italy.",
    "Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy.",
    "Medical Oncology, Breast & GYN Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) \"Dino Amadori\", Meldola, Italy.",
    "Department of Medical Oncology, \"S. Maria della Misericordia\" University Hospital, Azienda Sanitaria Universitaria Friuli Centrale, Udine, Italy.",
    "Clinical Trial Unit, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, Naples, Italy.",
    "U.O.C. Oncologia Medica-Ospedale Senatore Antonio Perrino, Brindisi, Italy.",
    "Department of Experimental Medicine, University of Salento, Fazzi Hospital, Lecce, Italy.",
    "Romagna Cancer Registry IRCCS Istituto Romagnolo per lo Studio dei Tumori \"Dino Amadori\" (IRST), Meldola, Italy.",
    "Department of Oncology, Hospital of Prato Azienda USL Toscana Centro, Prato, Italy.",
    "AOM Liguria, Azienda Ospedaliera Metropolitana di Genova, Genoa, Italy.",
    "Division of Anatomic Pathology and Cytopathology, Istituto Nazionale Tumori, IRCCS, Fondazione G. Pascale, Naples, Italy."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 26,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Anna Passarelli",
      "orcid": "0000-0003-4643-7809"
    },
    {
      "affs": [
        1
      ],
      "name": "Giovanni Luca Scaglione",
      "orcid": "0000-0001-5622-7843"
    },
    {
      "affs": [
        2
      ],
      "name": "Daniela Califano",
      "orcid": "0000-0001-6945-3209"
    },
    {
      "affs": [
        3
      ],
      "name": "Michele Bartoletti",
      "orcid": "0000-0002-9631-5693"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Domenica Lorusso",
      "orcid": "0000-0003-0981-0598"
    },
    {
      "affs": [
        0
      ],
      "name": "Sabrina Chiara Cecere"
    },
    {
      "affs": [
        6
      ],
      "name": "Anna Fagotti",
      "orcid": "0000-0001-5579-335X"
    },
    {
      "affs": [
        7
      ],
      "name": "Alberto Farolfi",
      "orcid": "0000-0002-3289-8041"
    },
    {
      "affs": [
        8
      ],
      "name": "Claudia Andreetta",
      "orcid": "0000-0002-0470-043X"
    },
    {
      "affs": [
        0
      ],
      "name": "Jole Ventriglia"
    },
    {
      "affs": [
        9
      ],
      "name": "Laura Arenare"
    },
    {
      "affs": [
        0
      ],
      "name": "Carmela Pisano"
    },
    {
      "affs": [
        2
      ],
      "name": "Daniela Russo"
    },
    {
      "affs": [
        6
      ],
      "name": "Maria Teresa Perri"
    },
    {
      "affs": [
        10
      ],
      "name": "Saverio Cinieri"
    },
    {
      "affs": [
        3
      ],
      "name": "Simona Scalone"
    },
    {
      "affs": [
        11
      ],
      "name": "Ugo De Giorgi",
      "orcid": "0000-0001-7520-2908"
    },
    {
      "affs": [
        12
      ],
      "name": "Valentina Arcangeli"
    },
    {
      "affs": [
        13
      ],
      "name": "Elena Zafarana"
    },
    {
      "affs": [
        6
      ],
      "name": "Maria Chiara Cannizzaro"
    },
    {
      "affs": [
        14
      ],
      "name": "Serafina Mammoliti",
      "orcid": "0000-0002-6560-0061"
    },
    {
      "affs": [
        2
      ],
      "name": "Tommaso Ambrosio"
    },
    {
      "affs": [
        15
      ],
      "name": "Rossella De Cecio"
    },
    {
      "affs": [
        9
      ],
      "name": "Clorinda Schettino"
    },
    {
      "affs": [
        9
      ],
      "name": "Francesco Perrone",
      "orcid": "0000-0002-9738-0526"
    },
    {
      "affs": [
        0
      ],
      "name": "Sandro Pignata",
      "orcid": "0000-0002-8836-2633"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2xt8zfjqw466g.bib",
  "cited_by": 0,
  "doi": "10.1200/po-26-00484",
  "fulltext_url": "https://europepmc.org/articles/PMC13704708",
  "id": "2xt8zfjqw466g",
  "issns": [
    "2473-4284"
  ],
  "landing_url": "https://europepmc.org/article/MED/42886889",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2729|Endometrial and Cervical Cancer Treatments"
    ]
  ],
  "openalex": "W7222531703",
  "pdf_url": "https://europepmc.org/articles/PMC13704708?pdf=render",
  "pmcid": "PMC13704708",
  "pmid": "42886889",
  "published": "2026-10-16",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/2xt8zfjqw466g.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:46Z",
      "native_id": "MED:42886889",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42886889"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2729|Endometrial and Cervical Cancer Treatments",
      "subfield": "reproductive-child"
    }
  ],
  "title": "PIK3CA Mutations in Advanced or Recurrent Endometrial Cancer: An Exploratory Molecular Profiling From the Phase II MITO END-3 Study.",
  "title_text": "PIK3CA Mutations in Advanced or Recurrent Endometrial Cancer: An Exploratory Molecular Profiling From the Phase II MITO END-3 Study.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:46Z",
  "url": "https://research.draconitic.com/paper/2xt8zfjqw466g",
  "venue": "JCO precision oncology",
  "versions": []
}