Open Access
REVIEW
Cancer and fibrosis: two different fates for a single player. Role of cytokines
Roberto Zefferino1,*, Annalucia Carbone2, Aglaja Zefferino2, Sante Di Gioia2, Massimo Conese2,*
1 Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
2 Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy
* Corresponding Author: Roberto Zefferino. Email: 
; Massimo Conese. Email: 
European Cytokine Network https://doi.org/10.32604/ecn.2026.079385
Received 20 January 2026; Accepted 02 July 2026; Published online 14 August 2026
Abstract
Cancer and fibrosis are two pathological conditions that although of different clinical appearance have several shared characteristics, most likely because of a common etiology (for example in case of Silica). Here, we present a comprehensive review of the literature, with respect to Crystalline Silica, a known carcinogenic and fibrogenic agent, aiming to highlight common denominators between both diseases, as well as their differences. The results from various studies point to the involvement of the immune response, cancer-associated fibroblasts (CAFs), cellular communication and various signaling pathways, including Notch, Wnt/β-catenin, and YAP/TAZ in their respective pathogenesis. In particular, pro-inflammatory cytokines are reported to trigger a stromal reaction mediated by adaptive immunity, leading to fibrosis. Conversely, an imbalance between the Treg and Teff cells alongside the activity of CAFs promotes cancer development. The Wnt/β-catenin pathway appears to play a pivotal role in these divergent responses. We propose a working hypothesis based on the mechanisms of action of silica and its effect with the perspective of developing targeted therapies for silica-induced disease.
Keywords
Microenvironment; Wnt/β-catenin; notch signaling; YAP/TAZ; silica; lung cancer; inflammation
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