HSP90-Specific nIR Probe Identifies Aggressive Prostate Cancers: Translation from Preclinical Models to a Human Phase I Study.

Journal Article (Journal Article)

A noninvasive test to discriminate indolent prostate cancers from lethal ones would focus treatment where necessary while reducing overtreatment. We exploited the known activity of heat shock protein 90 (Hsp90) as a chaperone critical for the function of numerous oncogenic drivers, including the androgen receptor and its variants, to detect aggressive prostate cancer. We linked a near-infrared fluorescing molecule to an HSP90 binding drug and demonstrated that this probe (designated HS196) was highly sensitive and specific for detecting implanted prostate cancer cell lines with greater uptake by more aggressive subtypes. In a phase I human study, systemically administered HS196 could be detected in malignant nodules within prostatectomy specimens. Single-cell RNA sequencing identified uptake of HS196 by malignant prostate epithelium from the peripheral zone (AMACR+ERG+EPCAM+ cells), including SYP+ neuroendocrine cells that are associated with therapeutic resistance and metastatic progression. A theranostic version of this molecule is under clinical testing.

Full Text

Duke Authors

Cited Authors

  • Osada, T; Crosby, EJ; Kaneko, K; Snyder, JC; Ginzel, JD; Acharya, CR; Yang, X-Y; Polascik, TJ; Spasojevic, I; Nelson, RC; Hobeika, A; Hartman, ZC; Neckers, LM; Rogatko, A; Hughes, PF; Huang, J; Morse, MA; Haystead, T; Lyerly, HK

Published Date

  • January 2022

Published In

Volume / Issue

  • 21 / 1

Start / End Page

  • 217 - 226

PubMed ID

  • 34675120

Pubmed Central ID

  • PMC8742774

Electronic International Standard Serial Number (EISSN)

  • 1538-8514

Digital Object Identifier (DOI)

  • 10.1158/1535-7163.MCT-21-0334

Language

  • eng

Conference Location

  • United States