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Heat shock protein 90 (Hsp90) inhibitors tethered to radioiodinated or optical probes for noninvasive breast cancer imaging

In vitro and mouse studies suggest Hsp90 inhibitors tethered to optical and radioiodinated probes could help detect and treat breast cancers. In breast cancer cells with ectopic expression of Hsp90, fluorophore-tethered Hsp90 inhibitors specifically bound surface-exposed Hsp90 and were internalized. In mice with breast cancer xenografts, radioiodinated Hsp90 inhibitors specifically accumulated in breast cancer cells and enabled noninvasive tumor imaging. Next steps include demonstrating that the probes selectively target the tumors over healthy tissues in microdosing trials in humans and exploring therapeutic approaches using tethered Hsp90 inhibitors.
Synta Pharmaceuticals Corp.'s Hsp90 inhibitor, ganetespib, is in Phase III testing to treat non-small cell lung cancer (NSCLC). The company has Hsp90 inhibitor-drug conjugates designed for tumor cell delivery in preclinical testing.
At least 13 other companies have Hsp90 inhibitors in Phase II or earlier testing to treat cancers.

SciBX 6(39); doi:10.1038/scibx.2013.1115
Published online Oct. 10, 2013

Patent application filed; available for licensing

Barrott, J.J. et al. Chem. Biol.; published online Sept. 12, 2013;
Contact: Timothy A. Haystead, Duke University, Durham, N.C.