Proteasome inhibitors therapeutic strategies for cancer.
Aberrations in the Ubiquitin-Proteasome System (UPS) have been recently connected to the pathogenesis of several human protein degradation disorders (e.g., cancer and neurodegenerative diseases), so that proteasome is now considered an important target for drug discovery. Small molecules able to inhibit and modulate UPS have been, in fact, described as novel tools for a new approach in anti-cancer therapy. In particular Proteasome Inhibitors (PIs), blocking activation of nuclear factor-kappa B (NF-kB), trigger a decreased cellular proliferation and angiogenic cytokine production, induce cell death and inhibit tumor cell adhesion to stroma. Furthermore, several studies have demonstrated that PIs potentiate the activity of other anti-cancer treatment, in part by down-regulating chemoresistance pathways. Therefore pharmacologic, preclinical, and clinical data suggested the use of PIs in anticancer strategies, for their potential therapeutic relevance in the treatment of cancer and inflammatory-related diseases. This review focuses on recent advances in the development of PIs anticancer agents highlighting both novel patented compounds and novel therapeutic protocol of intervention.
D'Alessandro
Annamaria
A
IRCCS-Fondazione Santa Lucia Centro di Ricerca sul Cervello, Rome, Italy.
Pieroni
Luisa
L
Ronci
Maurizio
M
D'Aguanno
Simona
S
Federici
Giorgio
G
Urbani
Andrea
A
D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D006801:Humans; D011480:Protease Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D061988:Proteasome Inhibitors
D020533:Angiogenesis Inhibitors; D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D011480:Protease Inhibitors; D061988:Proteasome Inhibitors