Thursday, October 10, 2013
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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.
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