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Two Novel Lilly Molecules Target Genetic Mutations That Can Lead to Cancer
Date:4/4/2011

heres – ultimately metastasizing, or spreading.

Lilly scientists focused on a growth factor called IL-6, which latches onto receptors on the surface of cells and triggers the IL-6–JAK–STAT3 signaling pathway, promoting formation of the deadly IBC cell clusters by activating the STAT3 protein, which then turns on the genes that encourage IBC cells to stick together.  

Researchers hypothesized that short-circuiting the IL-6–JAK–STAT3 pathway could prevent the formation of tumor cell clusters.  The scientists first cultured the tumor spheres in medium containing IL-6.  As expected, IL-6 activated STAT3, the cells proliferated, and the tumor spheres grew.  Furthermore, expression of IL-6 by the spheres themselves increased by 50-fold; and secretion of intracellularly produced IL-6 activated STAT3, and prevented cell death in the tumor spheres.

But when Lilly's JAK2 inhibitor was added to the medium containing the tumor spheres, the scientists found that it inhibited STAT3 activation in a dose-dependent manner and that blocking this signaling pathway induced cell death in the tumor spheres.  The IL-6–JAK–STAT3 pathway may serve as a "molecular signature" of IBC and as a potential therapeutic target.

Lilly's JAK2 inhibitor is currently being evaluated in Phase I clinical trials for the treatment of myeloproliferative neoplasms, or diseases of the blood and bone marrow, called polycythemia vera, essential thrombocythemia and myelofibrosis.  

LY2940680: Halting Abnormal Signaling via the Hedgehog Pathway (Abstract # 2819)

Lilly scientists have identified an orally administered anti-cancer agent, LY2940680, which, in preclinical studies, disrupted the abnormal signaling of a key regulator of embryonic cell development. Data was also presented at AACR's New Small Molecule Therapeutics mini-symposium.  

This novel molecule has been shown
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SOURCE Eli Lilly and Company
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