PRIN 2017 - 2017WLKYAM_003 - Resp. dr.ssa Alessandra Pescatore: Interfering with NF-kappaB ACTivation in human cancer (DSB.AD001.139)

Area tematica

Scienze biomediche

Area progettuale

Struttura responsabile del progetto di ricerca

Istituto di genetica e biofisica "Adriano Buzzati Traverso" (IGB)

Responsabile di progetto

ALESSANDRA PESCATORE
Telefono: +390816132257
E-mail: alessandra.pescatore@igb.cnr.it

Abstract

This proposal deals with the possibility to therapeutically target GADD45b in AML and thyroid carcinoma and with the role of GADD45b in regulating necroptosis. Gadd45b is a pro-survival factor regulated by NF-kB, able to block the sustained, pro-apoptotic JNK signaling, by means of its binding to MKK7. Interfering with the constitutive activation of NF-kB in cancer has been unsuccessfully attempted in the last decades due its pleiotropic roles. A more promising approach is represented by the development of inhibitors targeting downstream effectors of the NF-kB tumorigenic functions, such as Gadd45b. Our previous studies showed that GADD45b is a hallmark of aggressive cancer. Notably, the recently developed D-tripeptide inhibitor of the GADD45b/MKK7 interaction, DTP3, exhibits a potent and cancer-cell selective capacity to induce JNK-dependent apoptosis of Multiple Myeloma. Hence, we propose to assess the therapeutic efficacy of DTP3 in AML and thyroid carcinoma, for which safer and more effective therapies are urgently required. Indeed, the role of GADD45b in inhibiting not only apoptosis but also necroptosis will be evaluated, as the type of cancer PCD specifies whether [...]

Data inizio attività

29/08/2019

Parole chiave

Biological bases of cancer, Signal transduction, NF-kappaB

Ultimo aggiornamento: 13/12/2024