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

Lee, Esther K.; Martínez, María Carmen Riesco; Blakely, Kim M.; Santos, Keemo Delos; Hoang, Van; Chow, Annabelle; Emmenegger, Urban

doi:10.1016/j.mehy.2014.08.005

Cited by 19 publications

(13 citation statements)

References 72 publications

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“…In addition, the biochemical abnormalities were present prior to the administration of zoledronic acid (Table 1) and consequently the latter might have contributed rather than caused the electrolytic disturbances. This case was initially treatment-refractory most like due to massive renal phosphate losses secondary to oncogenic osteomalacia [5]. Vitamin D deficiency could be a possible cause for this biochemical picture.…”

Section: Discussionmentioning

confidence: 95%

“…At this stage, we considered denosumab, a monoclonal antibody, which inhibits the human receptor activator of nuclear factor kappa-B ligand (RANKL). Nonetheless, denosumab was withheld because it could potentially cause severe Abbreviations: CT chemotherapy, Z zoledronic acid, ET endocrine treatment, FGF23 fibroblast growth factor 23, ALP alkaline phosphatase, PTH parathyroid hormone, 25-HD 25-hydroxyvitamin D, CEA carcinoembryonic antigen § results obtained 6 days after the administration of zoledronic acid; ¶ results obtained 3 weeks after the administration of zoledronic acid hypocalcaemia and hypophosphataemia on the background of active oncogenic osteomalacia [5].…”

Section: Case Presentationmentioning

confidence: 99%

See 1 more Smart Citation

Oncogenic osteomalacia and metastatic breast cancer: a case report and review of the literature

Savva

Adhikaree

Madhusudan

et al. 2019

J Diabetes Metab Disord

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Objectives Oncogenic osteomalacia is a rare paraneoplastic metabolic syndrome that is characterised by severe hypophosphataemia, hyperphosphaturia and osteomalacia secondary to renal loss of phosphate. It is commonly caused by overproduction of fibroblast growth factor-23 (FGF23) from benign tumours of mesenchymal origin. Currently, there is no clear evidence on the management of oncogenic osteomalacia in patients with metastatic solid tumours. Methods We report a case of breast cancer-induced oncogenic osteomalacia and discuss its diagnosis and management. Results A 71-year-old woman with advanced breast cancer developed symptomatic oncogenic osteomalacia with raised FGF23, severe hypophosphataemia and hypocalcaemia. The electrolytic disturbances were exacerbated after the administration of bisphosphonates in the context of her oncological treatment. Systemic chemotherapy and maintenance endocrine treatment along with phosphate and calcium supplementation reduced the activity of oncogenic osteomalacia and resolved the electrolytic imbalances. Conclusions To our knowledge, this is the first reported case of oncogenic osteomalacia in a patient with breast cancer. Oncogenic osteomalacia constitutes a diagnostic and therapeutic challenge. Pre-clinical and clinical evidence suggest that a possible underlying mechanism is the presence of molecular alterations in the FGF/FGFR signalling pathway leading to overexpression of FGF23. In metastatic setting, anticancer treatment can potentially lead to the normalisation of the electrolytic disturbances and reduction of the activity of oncogenic osteomalacia. The use of antiresorptive therapy in patients with bone metastases can potentially trigger FGF23 overexpression. Its use should be guided by the patients' risk of skeletal-related events and electrolytic disturbances as well as the degree of activity of oncogenic osteomalacia.

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Section: Discussionmentioning

confidence: 95%

Section: Case Presentationmentioning

confidence: 99%

Oncogenic osteomalacia and metastatic breast cancer: a case report and review of the literature

Savva

Adhikaree

Madhusudan

et al. 2019

J Diabetes Metab Disord

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“…Elevated FGF-23 is observed in an adenocarcinoma with an aactivating somatic KRAS mutation (G12V), suggesting that RAS can regulate FGF-23 ectopically in non-osseous tissues. Prostate and colon cancer can also cause hypophosphatemia through ectopic production of FGF-23 [41, 42]. …”

Section: Hereditary Diseases Caused By Fgf-23mentioning

confidence: 99%

Multiple faces of fibroblast growth factor-23

Han

Quarles²

2016

Current Opinion in Nephrology and Hypertension

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Purpose of the review This review examines therole of FGF-23 in mineral metabolism, innate immunity and adverse cardiovascular outcomes. Recent findings FGF-23, produced by osteocytes in bone, activates FGFR/α-Klotho complexes in the kidney. The resulting bone-kidney axis coordinates renal phosphate reabsorption with bone mineralization, and creates a counter-regulatory feedback loop to prevent vitamin D toxicity. FGF-23 acts to counter-regulate the effects of Vitamin D on innate immunity and cardiovascular responses. FGF-23 is ectopically expressed along with α-Klotho in activated macrophages, creating a pro-inflammatory paracrine signaling pathway that counters the anti-inflammatory actions of vitamin D. FGF-23 also inhibits ACE2 expression and increases sodium reabsorption in the kidney, leading to hypertension and left ventricular hypertrophy. Finally, FGF-23 is purported to cause adverse cardiac and impair neutrophil responses through activation of FGFRs in the absence of α-Klotho. While secreted forms of α-Klotho have FGF-23- independent effects, the possibility of α-Klotho-independent effects of FGF-23 is controversial and requires additional experimental validation. Summary FGF-23 participates in a bone-kidney axis regulating mineral homeostasis, proinflammatory paracrine macrophage signaling pathways, and in a bone-cardio-renal axis regulating hemodynamics that counteract the effects of Vitamin D.

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“…Given that bone is by far the most common site of PCa metastasis, this may be clinically significant. Lee et al [ 25 ] have observed severe hypophosphatemia in a subgroup of patients with advanced PCa consistent with excess FGF23 activity and also report a bioinformatics analysis showing increased FGF23 mRNA expression in a subset of patients with metastatic PCa. These results complement our observations in localized PCa and the biological studies reported here.…”

Section: Discussionmentioning

confidence: 93%

FGF23 promotes prostate cancer progression

et al. 2015

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Prostate cancer is the most common cancer in US men and the second leading cause of cancer deaths. Fibroblast growth factor 23 (FGF23) is an endocrine FGF, normally expressed by osteocytes, which plays a critical role in phosphate homeostasis via a feedback loop involving the kidney and vitamin D. We now show that FGF23 is expressed as an autocrine growth factor in all prostate cancer cell lines tested and is present at increased levels in prostate cancer tissues. Exogenous FGF23 enhances proliferation, invasion and anchorage independent growth in vitro while FGF23 knockdown in prostate cancer cell lines decreases these phenotypes. FGF23 knockdown also decreases tumor growth in vivo. Given that classical FGFs and FGF19 are also increased in prostate cancer, we analyzed expression microarrays hybridized with RNAs from of LNCaP cells stimulated with FGF2, FGF19 or FGF23. The different FGF ligands induce overlapping as well as unique patterns of gene expression changes and thus are not redundant. We identified multiple genes whose expression is altered by FGF23 that are associated with prostate cancer initiation and progression. Thus FGF23 can potentially also act as an autocrine, paracrine and/or endocrine growth factor in prostate cancer that can promote prostate cancer progression.

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

Cited by 19 publications

References 72 publications

Oncogenic osteomalacia and metastatic breast cancer: a case report and review of the literature

Oncogenic osteomalacia and metastatic breast cancer: a case report and review of the literature

Multiple faces of fibroblast growth factor-23

FGF23 promotes prostate cancer progression

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