Targeting metabolic and epigenetic reprogramming in metastatic fumarate hydratase-deficient renal cell carcinoma

Kührer N, Huebner-Resch I, Mayr R, Agaimy A, Kronbichler A, Hartmann A, Schmidinger M, Pichler R (2025)

Publication Language: English

Publication Type: Journal article, Review article

Publication year: 2025

Journal

Clinical & Experimental Metastasis Springer Verlag (Germany)

Book Volume: 42

Article Number: 47

Journal Issue: 5

DOI: 10.1007/s10585-025-10368-9

Abstract

Fumarate hydratase-deficient renal cell carcinoma (FHdRCC) has been classified under the new category of molecularly defined RCCs according to the WHO classification 2022. Although rare, FHdRCC is an aggressive malignancy with a high metastatic potential and poor prognosis, even at early stages. Due to its low incidence, no standard therapeutic regimen has been established to date. Several phase 2 clinical trials are evaluating combinations of targeted therapies in patients with advanced/metastatic disease. These include immune checkpoint inhibitors (nivolumab, tislelizumab, sintilimab, avelumab), multi-tyrosine kinase inhibitors (cabozantinib, erlotinib, lenvatinib, axitinib, vandetanib), and PARP inhibitors (talazoparib). The most promising combinations are nivolumab/cabozantinib (N = 5, objective response rate (ORR): 100%), lenvatinib/tislelizumab (N = 14, ORR: 93.3%), bevacizumab/erlotinib (N = 43, ORR: 72%), and sintilimab/axitinib (N = 19, ORR: 63.1%). In this review, we will provide a detailed overview of ongoing clinical trials, highlighting the roles of metabolic and epigenetic reprogramming, as well as pro- oncogenic signaling, which together form the backbone for emerging novel targeted treatment strategies. Targeting these specific signaling pathways will shift the therapeutic landscape toward personalized medicine in metastatic FHdRCC.

Authors with CRIS profile

Abbas Agaimy Institute of Pathology Arndt Hartmann Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie

Involved external institutions

Universität Regensburg DE Germany (DE) Medizinische Universität Innsbruck AT Austria (AT) Medizinische Universität Wien AT Austria (AT)

How to cite

APA:

Kührer, N., Huebner-Resch, I., Mayr, R., Agaimy, A., Kronbichler, A., Hartmann, A.,... Pichler, R. (2025). Targeting metabolic and epigenetic reprogramming in metastatic fumarate hydratase-deficient renal cell carcinoma. Clinical & Experimental Metastasis, 42(5). https://doi.org/10.1007/s10585-025-10368-9

MLA:

Kührer, Nadja, et al. "Targeting metabolic and epigenetic reprogramming in metastatic fumarate hydratase-deficient renal cell carcinoma." Clinical & Experimental Metastasis 42.5 (2025).

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