Quantitative analysis of taxane drug target engagement of microtubules in circulating tumor cells from metastatic castration resistant prostate cancer patients treated with CRXL301, a nanoparticle of docetaxel.

ABSTRACT:

Aim

We reviewed the radiographic response of three patients with metastatic castration-resistant prostate cancer treated with CRXL301, a docetaxel nanoparticle. For these three patients, we isolated and analyzed circulating tumor cells (CTCs) to explore microtubule (MT) drug-target engagement (MT-DTE) as a biomarker of response to treatment. MT-DTE was based on a quantitative assessment of the MT cytoskeleton in CTCs from pre- and post-treatment patient samples as a potential read-out of CRXL301 activity.

Methods

We isolated CTCs using negative CD45⁺ depletion and subjected them to multiplex confocal microscopy using our established protocol. CTCs were identified as CD45^-/CK⁺/DAPI⁺ cells and MT-DTE was determined using our develope

SUBMITTER: Mukhtar E 

PROVIDER: S-EPMC7556717 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature