A gain-of-function mutation in Janus kinase 2 (JAK2V617F) is at the basis of the majority of chronic myeloproliferative neoplasms (MPN). Enhanced activation of other downstream pathways including the PI3K/mTOR pathway has been documented as well. In this study we evaluated the effects of JAK1/2 inhibitors, alone and in combination with mTOR, with a dual mTOR/PI3K inhibitor and with a pan PI3K inhibitor in in-vitro and in-vivo MPN models. Our findings of strong synergy between the JAK2 inhibitors and mTOR/PI3K inhibitor suggested that we might be able to administer these drugs at lower concentrations than when the drugs are used individually. This provides a framework for combination trials using compounds in patients with myeloproliferative neoplasms
University of Florence, Italy
Titolo del libro
Study of intracellular signaling pathways in Chronic Myeloproliferative Neoplasms
Autori
Serena Martinelli
Opera sottoposta a peer review
Numero di pagine
80
Anno di pubblicazione
2017
Copyright
© 2017 Author(s)
Licenza d'uso
Licenza dei metadati
Editore
Firenze University Press
DOI
10.36253/978-88-6453-565-4
ISBN Print
978-88-6453-564-7
eISBN (pdf)
978-88-6453-565-4
eISBN (xml)
978-88-9273-168-4
Collana
Premio Tesi di Dottorato
ISSN della collana
2612-8039
e-ISSN della collana
2612-8020