Titre : Targeting STAT3 Protein-Protein Interactions with Small Molecules:
Therapeutics for Treating Cancer.

*** Attention, la conférence aura lieu exceptionnellement à 15 h au G-715 ***

La conférence sera prononcée (en anglais) par le professeur Patrick Gunning, du département des sciences chimique et physique de l'University of Toronto-Mississauga.

Résumé : STAT3 protein-protein interactions are essential for transducing signals from extracellular stimuli, but also functions as a nuclear transcription factor required for regulating genes involved in proliferation, apoptosis, angiogenesis and invasion, in addition to genes encoding cytokines,chemokines and growth factors. In contrast to the transient nature of STAT3 activation in normal cells, many humancancers, including breast, prostate, ovarian, brain and multiple myeloma (MM) harbor constitutive STAT3 activity. STAT3 downstream target genes are critical to the dysregulated biological processes that promote tumor cell growth, survival and induce chemoresistance, thus targeting STAT3 signaling represents an important therapeutic target in cancer therapy.

We have rationally designed and developed STAT3 inhibitors that disrupt transcriptionaly active STAT3­-STAT3 homo-dimers, suppress STAT3 activation (phosphorylation), inhibit STAT3-target gene expression (c-Myc, Bcl-xL, survivin) and potently induce apoptosis in tumor cells harboring aberrant STAT3 activity. Moreover, lead compound SH-4-54, a small molecule inhibitor, induced strong antitumor effects on human breast cancer, multiple myeloma and brain cancer preclinical tumor models. Most notably, SH-4-54 is orally bioavailable, strongly inhibiting the growth of tumors, identifying it as a most potent orally bioavailable
STAT3-targeting inhibitor.

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