Abstract

Abstract In our previous paper, propranolol is used in hemangioblastomas primary cultures from patients with von Hippel- Lindau disease. This is a rare inherited oncologic condition characterized by the growth of tumors affecting mainly the central nervous system, but also kidneys, pancreas, adrenal glands, retinas and endolymphatic sacs (inner ear). Up to date, the only treatment for these patients is surgery. The search for drugs able, at least, to stop the development of hemangioblastomas, has led our group to propose propranolol, a non-specific beta blocker, as a drug to test. According to the results of this work, propranolol would act by decreasing hypoxia signaling pathway, which is constitutively active in VHL patients, normalizing the hypoxia target genes involved in angiogenesis, survival and stemness in the hemangioblastoma cells. The results in vitro are promising and, in the absence of serious side effects, propranolol could be assayed as a therapy in the clinical practice for VHL patients.

Highlights

  • Von Hippel-Lindau (VHL) disease is a rare type of oncological disease with an incidence of 1/36,000 individuals in the general population [1,2]

  • Tumors develop when a loss of heterozygosity occurs in addition to the mutated copy of VHL at birth [8]. pVHL binds to HIF-1α and HIF-2α targeting them for degradation in the proteasome [9]

  • In the absence of functional pVHL HIF accumulates and translocates to the nucleus triggering the hypoxia responsive genes program involved in cell proliferation, angiogenesis, extracellular matrix degradation, vascular tone, stemness and glycolytic metabolism

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Summary

Introduction

Von Hippel-Lindau (VHL) disease is a rare type of oncological disease with an incidence of 1/36,000 individuals in the general population [1,2]. In the absence of functional pVHL HIF accumulates and translocates to the nucleus triggering the hypoxia responsive genes program involved in cell proliferation, angiogenesis, extracellular matrix degradation, vascular tone, stemness and glycolytic metabolism. Cells from VHL tumors have a constitutively active HIF program due to the absence of functional pVHL.

Results
Conclusion

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