Details

Autor(en) / Beteiligte

• Yuno, Akira
• Lee, Min-Jung
• Lee, Sunmin
• Tomita, Yusuke
• Rekhtman, David
• Moore, Brittni
• Trepel, Jane B

Titel

Clinical Evaluation and Biomarker Profiling of Hsp90 Inhibitors

Ist Teil von

• Methods in molecular biology (Clifton, N.J.), 2018, Vol.1709, p.423

Ort / Verlag

United States

Erscheinungsjahr

2018

Quelle

MEDLINE

Beschreibungen/Notizen

• Inhibitors of the molecular chaperone heat shock protein 90 (Hsp90) have been in clinical development as anticancer agents since 1998. There have been 18 Hsp90 inhibitors (Hsp90i) that have entered the clinic, all of which, though structurally distinct, target the ATP-binding Bergerat fold of the chaperone N-terminus. Currently, there are five Hsp90 inhibitors in clinical trial and no approved drug in this class. One impediment to development of a clinically efficacious Hsp90 inhibitor has been the very low percentage of clinical trials that have codeveloped a predictive or pharmacodynamic marker of the anticancer activity inherent in this class of drugs. Here, we provide an overview of the clinical development of Hsp90 inhibitors, review the pharmacodynamic assays that have been employed in the past, and highlight new approaches to Hsp90 inhibitor clinical development.