NCT02873832

Efficacy of Heat-shock Protein (HSP) Inhibitors in Myeloproliferative Syndromes (MPS)

Efficacy of Heat-shock Protein (HSP) Inhibitors in Myeloproliferative Syndromes (MPS): Fundamental Observational in Vitro Study Using Samples From a Collection

• Status: Completed
• Phase: —
• Study type: Observational
• Enrollment: 37 (actual)
• Sponsor: Centre Hospitalier Universitaire Dijon · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Heat-shock proteins (HSP) have been very highly conserved throughout the evolution of species and are characterized by their chaperone function, thanks to their ability to prevent aggregation and to promote the renaturation/break down of damaged proteins. Among other targets, they also chaperone JAK2, a key step that is deregulated in signalling in myeloproliferative syndromes (MPS) because of the JAK2V617F mutation. These HSP also have a potent cytoprotective action through their multiples inhibiting effects on apoptotic processes. Little is known about levels of HSP expression, in particular for HSP70 and HSP27, in MPS cells. However, in vitro studies of different cell models have shown the interest of HSP90 inhibitors in slowing cell proliferation in MPS. These results have been confirmed in animal models with results in terms of blood counts and overall survival. In addition, it seems that the V617F mutated form of JAK2 is more sensitive than the wild-type to HSP90 inhibitors. Finally, inhibitors of HSP90 remain efficacious with regard to the inhibition of cell growth, even in cases of resistance to JAK2 inhibitors. Nonetheless, HSP90 inhibitors are known to stimulate the expression of other HSP, notably HSP27 and HSP70, which are, through their properties, tumorigenic and could lead to an escape phenomenon. Thus the combined use of several HSP inhibitors could be beneficial, and eventually present synergistic effects on the inhibition of tumour processes.

Conditions

• Myeloproliferative Syndrome

Interventions

Type	Name	Description
BIOLOGICAL	Blood sample
OTHER	Flow cytometry
OTHER	western blot

Timeline

• Start date: 2015-01-01
• Primary completion: 2016-04-01
• First posted: 2016-08-22
• Last updated: 2016-08-22

Locations

1 site across 1 country: France