{
  "abstract": "Ovarian cancer (OC) is often diagnosed at advanced stages, and resistance to platinum-based chemotherapy remains one of the leading causes of treatment failure. This resistance is sustained in part by metabolic plasticity, particularly through the de novo serine synthesis pathway (SSP), orchestrated by D-3-phosphoglycerate dehydrogenase (PHGDH), which diverts glycolytic carbon toward serine, glycine, and one-carbon (1C) units that fuel nucleotide biosynthesis, epigenetic regulation, and redox homeostasis. Elevated PHGDH expression in OC is associated with advanced International Federation of Gynecology and Obstetrics (FIGO) stage and poorer overall survival; conversely, a subset of tumors downregulates PHGDH at relapse and shifts toward NAD+-dependent pathways that sustain poly(ADP-ribose) polymerase (PARP) activity and DNA repair, creating a distinct therapeutic vulnerability. Rather than a contradiction, this bidirectional behavior reflects the metabolic plasticity through which OC adapts to treatment pressure. Therefore, this review analyzes the context-dependent role of PHGDH in OC, the mechanistic basis of divergent associations with therapy resistance, and the current status of pharmacological inhibitors. Preclinical evidence indicates that PHGDH inhibition with CBR-5884 increases oxidative stress, reduces stemness, and restores platinum sensitivity in PHGDH-high models. We further identify the relationship between PHGDH and radiotherapy response as an unexplored question in OC, despite evidence of SSP-dependent radioresistance in other tumor types. Together, these observations position PHGDH as an actionable, but biomarker-dependent, metabolic target in OC.",
  "abstract_shown": true,
  "affiliations": [
    "Laboratorio de Biomedicina Molecular, Facultad de Ciencias Químico-Biológicas, Universidad Autónoma de Guerrero, Av. Lázaro Cárdenas S/N Sede Sur, El Centenario, Chilpancingo 39090, Mexico",
    "Clínica de Cáncer Hereditario—Instituto Nacional de Cancerología, Av. San Fernando 22, Belisario Domínguez Secc 16, Tlalpan, Ciudad de Mexico 14080, Mexico",
    "Programa Investigadores por México—Secretaría de Ciencia, Humanidades, Tecnología e Innovación (SECIHTI), Av. Insurgentes Centro 1582, Crédito Constructor, Benito Juárez, Ciudad de Mexico 03940, Mexico"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jesús Omar Velázquez-Moreno",
      "orcid": "0009-0003-3520-4329"
    },
    {
      "affs": [
        1
      ],
      "name": "María de la Luz Mejía-Aguayo",
      "orcid": "0009-0000-2298-9719"
    },
    {
      "affs": [
        0
      ],
      "name": "Felix De Dios Padre Casarrubias-Jaimes"
    },
    {
      "affs": [
        1
      ],
      "name": "Marcela Angélica De la Fuente-Hernández"
    },
    {
      "affs": [
        0
      ],
      "name": "Daniel de Jesús Apolonio-Sánchez"
    },
    {
      "affs": [
        1
      ],
      "name": "Rodrigo Sosa-León",
      "orcid": "0009-0002-6533-2076"
    },
    {
      "affs": [
        1
      ],
      "name": "Rosa María Álvarez-Gómez"
    },
    {
      "affs": [
        0
      ],
      "name": "Marco Antonio Leyva-Vázquez",
      "orcid": "0000-0002-3345-5859"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Abraham Pedroza-Torres"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Olga Lilia Garibay-Cerdenares",
      "orcid": "0000-0002-0986-9453"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6z1jb25xtkn2k.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms27219535",
  "fulltext_url": null,
  "id": "6z1jb25xtkn2k",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://www.mdpi.com/1422-0067/27/21/9535",
  "language": null,
  "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": [
    [
      "openalex",
      "1306|Cancer, Hypoxia, and Metabolism"
    ]
  ],
  "openalex": "W7223818240",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-25",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/6z1jb25xtkn2k.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:57Z",
      "native_id": "10.3390/ijms27219535",
      "source": "crossref",
      "url": "https://www.mdpi.com/1422-0067/27/21/9535"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:1306|Cancer, Hypoxia, and Metabolism",
      "subfield": "oncology"
    }
  ],
  "title": "The Role of D-3-Phosphoglycerate Dehydrogenase (PHGDH) in Chemoresistance in Ovarian Cancer: Molecular Insights and Therapeutic Potential",
  "title_text": "The Role of D-3-Phosphoglycerate Dehydrogenase (PHGDH) in Chemoresistance in Ovarian Cancer: Molecular Insights and Therapeutic Potential",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:57Z",
  "url": "https://research.draconitic.com/paper/6z1jb25xtkn2k",
  "venue": "International Journal of Molecular Sciences",
  "versions": []
}