Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/223113
Title: The Multifaceted Role of Growth Differentiation Factor 15 (GDF15): A Narrative Review from Cancer Cachexia to Target Therapy
Author: Filippini, Daria Maria
Romaniello, Donatella
Carosi, Francesca
Fabbri, Laura
Carlini, Andrea
Giusti, Raffaele
Maio, Massimo di
Alfieri, Salvatore
Lauriola, Mattia
Pantaleo, Maria A.
Arribas, Lorena
Oliva Bernal, Marc
Bossi, Paolo
Locati, Laura Deborah
Keywords: Marcadors tumorals
Oncologia
Tumor markers
Oncology
Issue Date: 8-Aug-2025
Publisher: MDPI
Abstract: Background: Growth Differentiation Factor 15 (GDF15) has emerged as a key biomarker and therapeutic target in oncology, with roles extending beyond cancer cachexia. Elevated GDF15 levels correlate with poor prognosis across several solid tumors, including colorectal, gastric, pancreatic, breast, lung, prostate, and head and neck cancers. GDF15 modulates tumor progression through PI3K/AKT, MAPK/ERK, and SMAD2/3 signaling, thereby promoting epithelial-to-mesenchymal transition, metastasis, immune evasion, and chemoresistance via Nrf2 stabilization and oxidative stress regulation. Methods: We performed a narrative review of the literature focusing on the role of GDF15 in solid tumors, with a particular emphasis on head and neck cancers. Results: In head and neck squamous cell carcinoma (HNSCC), GDF15 overexpression is linked to aggressive phenotypes, radioresistance, poor response to induction chemotherapy, and failure of immune checkpoint inhibitors (ICIs). Similar associations are observed in colorectal, pancreatic, and prostate cancer, where GDF15 contributes to metastasis and therapy resistance. Targeting the GDF15-GFRAL axis appears therapeutically promising: the monoclonal antibody ponsegromab improved cachexia-related outcomes in the PROACC-1 trial, while visugromab combined with nivolumab enhanced immune response in ICI-refractory tumors. Conclusions: Further investigation is warranted to delineate the role of GDF15 across malignancies, refine patient selection, and evaluate combinatorial approaches with existing treatments.
Note: Reproducció del document publicat a: https://doi.org/10.3390/biomedicines13081931
It is part of: Biomedicines, 2025, vol. 13, num. 8, 1931
URI: https://hdl.handle.net/2445/223113
Related resource: https://doi.org/10.3390/biomedicines13081931
ISSN: 2227-9059
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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