Repurposing a psychoactive drug for children with cancer: p27^Kip1-dependent inhibition of metastatic neuroblastomas by Prozac.

ABSTRACT: The MYC family of transcription factors is a major driver of human cancer and potential therapeutic target. However, no clinically viable drugs have been yet developed that are able to directly tackle MYC oncoproteins. In our laboratory, we are exploring alternative approaches aiming to disturb signalling downstream of MYC. MYCN is frequently activated in neuroblastoma, a paediatric solid malignancy that, in its metastatic form, has a very poor prognosis. An important pathway regulated by MYC is the CKS1/SKP2/p27^kip1 axis. In this study, we have repurposed the anti-psychotic drug Prozac to disrupt CKS1/SKP2/p27^Kip1 signalling and assess its potential as an anti-neuroblastoma agent in vitro and in vivo. Using DNA editing technology, we show that stabilisation of p27

SUBMITTER: Bibbo' S 

PROVIDER: S-EPMC6949307 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature