FGF23: mediator of poor prognosis in a sizeable subgroup of patients with castration-resistant prostate cancer presenting with severe hypophosphatemia?

Med Hypotheses

Biological Sciences, Sunnybrook Research Institute, University of Toronto, ON, Canada; Medical Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, ON, Canada; Institute of Medical Science, University of Toronto, ON, Canada. Electronic address:

Published: October 2014

Castration-resistant prostate cancer (CRPC) is an advanced and incurable stage of the second most frequently diagnosed malignancy in men globally. Current treatment options improve survival modestly but eventually fail due to intrinsic or acquired therapeutic resistance. A hypothesis is presented wherein circulating levels of fibroblast growth factor 23 (FGF23), an endocrine member of the fibroblast growth factor family with phosphaturic properties, are proposed as a prognostic and predictive marker to identify CRPC patients with poor prognosis that are amenable to FGF23 antibody therapy (FGF23i) or treatment with fibroblast growth factor receptor inhibitors (FGFRi). With respect to the latter, FGF23 may also serve as a pharmacodynamic marker enabling individualized FGFRi dosing. We recently discovered that the development of severe and sustained hypophosphatemia in CRPC patients undergoing zoledronic acid therapy for bone metastases was associated with markedly worse prognosis compared to patients without or with only mild and transient hypophosphatemia. Severe hypophosphatemia is a typical manifestation of tumor-induced hypophosphatemic osteomalacia (TIO), a paraneoplastic condition mediated by FGF23 overexpression in most instances. While the postulated tumor-promoting role of FGF23 in CRPC or other malignancies has not yet been studied, several lines of evidence suggest that FGF23 may mediate both severe hypophosphatemia (via its endocrine properties) and aggressive CRPC behavior (via autocrine and paracrine activities): (i) FGF23 and the necessary signalling machinery (i.e. members of the fibroblast growth factor receptor [FGFR] family and the essential co-receptor α-KLOTHO [KL]) are highly expressed in a sizeable subgroup of CRPC patients; (ii) FGF/FGFR signalling plays important roles in prostate cancer; (iii) FGF23 can induce its own expression via a positive autocrine feedback loop involving FGFR1; and (iv) this positive feedback loop may be triggered by bone-targeted therapies frequently used for the treatment of CRPC-associated bone metastases. While there is a lack of personalized treatment strategies in the management of CRPC to date, FGF23 targeted therapy has the potential to fill this unmet clinical need in the not-so-distant future. In fact, FGFRi are currently in advanced clinical testing for a number of malignancies such as kidney and lung cancer, but there is a lack of conclusive data on FGFRi therapy in patients selected for FGF/FGFR pathway activation.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.mehy.2014.08.005DOI Listing

Publication Analysis

Top Keywords

fibroblast growth
16
growth factor
16
prostate cancer
12
crpc patients
12
fgf23
10
poor prognosis
8
sizeable subgroup
8
castration-resistant prostate
8
factor receptor
8
bone metastases
8

Similar Publications

Obstructive sleep apnea (OSA) is increasingly recognized for its link to idiopathic pulmonary fibrosis (IPF), though the underlying mechanisms remain poorly understood. Histone lysine demethylase 6B (KDM6B) may either prevent or promote organ fibrosis, but its specific role in IPF is yet to be clarified. This study aimed to investigate the function and mechanisms of KDM6B in IPF and the exacerbating effects of OSA.

View Article and Find Full Text PDF

Deficiency of Epithelial PIEZO1 Alleviates Liver Steatosis Induced by High-Fat Diet in Mice.

Int J Biol Sci

January 2025

Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

PIEZO1 has been found to play a vital role in regulating intestinal epithelial cells (IEC) function and maintaining intestinal barrier in recent years. Therefore, IEC PIEZO1 might exert a significant impact on liver metabolism through the gut-liver axis, but there is no research on this topic currently. Classic high-fat diet (HFD) model and mice with IEC-specific deficiency of PIEZO1 ( ) were used to explore the problem.

View Article and Find Full Text PDF

The present study aimed to investigate the role of a recombinant protein based on human collagen type I (RCPhC1) as a scaffold in maintaining the human tumor microenvironment within a patient-derived tumor xenograft (PDTX) model. RCPhC1, synthesized under animal component-free conditions, was explored for its potential to support the human-specific stroma associated with tumor growth. PDTX models were established using resected colorectal cancer liver metastasis specimens, and stromal cell populations from humans and mice were compared using three scaffolds: No scaffold (control), Matrigel and recombinant human collagen type I, across two passages.

View Article and Find Full Text PDF

Background: Skin pigmentation disorders may increase patients' psychological burdens. Consequently, they are increasingly attracting attention. Dermal fibroblasts have been shown to regulate pigmentation by secreting soluble factors.

View Article and Find Full Text PDF

Ultraviolet (UV) irradiation is a major factor contributing to skin photoaging, including the formation of reactive oxygen species (ROS), collagen breakdown, and overall skin damage. Insulin-like growth factor-I (IGF-1) is a polypeptide hormone that regulates dermal survival and collagen synthesis. Echinacoside (Ech), a natural phenylethanoid glycoside, is the most abundant active compound in Cistanches.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!