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Molecular-Guided Precision Oncology in Cancer of Unknown Primaryv : A State-of-the-Art Perspective

Title: Molecular-Guided Precision Oncology in Cancer of Unknown Primaryv : A State-of-the-Art Perspective
Authors: Subbiah, Vivek; Rassy, Elie; A. Greco, Frank
Contributors: Sarah Cannon Research Institute Nashville, Tennessee; Centre de recherche en épidémiologie et santé des populations (CESP); Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse; AP-HP. Université Paris Saclay-AP-HP. Université Paris Saclay-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay; Département de médecine oncologique Gustave Roussy (DMO); Institut Gustave Roussy (IGR)
Source: ISSN: 2075-4426 ; Journal of Personalized Medicine ; https://hal.science/hal-05502979 ; Journal of Personalized Medicine, 2026, 16 (2), pp.80-80. ⟨10.3390/jpm16020080⟩.
Publisher Information: CCSD; MDPI
Publication Year: 2026
Collection: Université de Versailles Saint-Quentin-en-Yvelines: HAL-UVSQ
Subject Terms: Genomic information; Perspective (graphical); Personalized medicine; Occult; Cancer; Clinical trial; Liquid biopsy; Precision oncology; Precision medicine; [SDV]Life Sciences [q-bio]
Description: International audience ; Cancer of unknown primary (CUP) is evolving from a diagnosis of exclusion treated with empirical chemotherapy to a molecularly defined entity amenable to precision-based interventions. This heterogeneous entity, comprising 2–3% of all metastatic malignancies, encompasses diverse cancers with clinically occult primary sites at diagnosis after a thorough workup. Recent landmark trials including CUPISCO and Fudan CUP-001 have demonstrated significant survival improvements with molecularly guided therapies compared to empirical chemotherapy, fundamentally enhancing and complementing traditional organ-centric treatment paradigms. This review synthesizes the current evidence supporting molecular diagnostics, tumor-agnostic therapies, and precision-based approaches in CUP management. We examine the clinical utility of comprehensive genomic profiling, gene expression profiling, and liquid biopsy technologies, while addressing implementation challenges and future directions. The integration of molecular tumor boards and the emergence of tissue/tissue-of-origin agnostic therapies herald a new era where CUP transitions from therapeutic nihilism to personalized oncology. As molecular technologies advance and targeted therapies proliferate, CUP may no longer represent a diagnosis of exclusion but rather an opportunity for molecularly informed precision care.
Document Type: article in journal/newspaper
Language: English
Relation: info:eu-repo/semantics/altIdentifier/pmid/41745373; PUBMED: 41745373; PUBMEDCENTRAL: PMC12941490
DOI: 10.3390/jpm16020080
Availability: https://hal.science/hal-05502979; https://hal.science/hal-05502979v1/document; https://hal.science/hal-05502979v1/file/jpm-16-00080.pdf; https://doi.org/10.3390/jpm16020080
Rights: https://creativecommons.org/licenses/by/4.0/ ; info:eu-repo/semantics/OpenAccess
Accession Number: edsbas.BE9DBAC3
Database: BASE