ArticleCancer drug resistance (Alhambra, Calif.)2020
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.
Article in Cancer drug resistance (Alhambra, Calif.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 6 citations in OpenAlex.
- Preclinical Investigation of PLGA Nanocapsules and Nanostructured Lipid Carriers for Organoselenium Delivery: Comparative In Vitro Toxicological Profile and Anticancer Insights.Pharmaceutics · 2025Article
- Stimulus-responsive self-assembled prodrugs in cancer therapy.Chemical science · 2022Review
- Cyclodextrin nanoparticles for diagnosis and potential cancer therapy: A systematic review.Frontiers in cell and developmental biology · 2022Review
- Phytochemical-Based Nanomedicine for Advanced Cancer Theranostics: Perspectives on Clinical Trials to Clinical Use.International journal of nanomedicine · 2020Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
aimWe 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.
methodsWe isolated CTCs using negative CD45
resultsWe collected CTCs at seven time points from three metastatic castration-resistant prostate cancer patients. Clinical response was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 criteria in those patients with measurable disease. Of the three patients enrolled, one experienced partial response (-50%) to CRXL301 and two patients were unevaluable given bone only disease. Notably, however, these two patients showed stable disease clinically based on bone scans. MT-DTE across all time points revealed that, early time points within four and 24 h of drug administration exhibited the highest levels of drug engagement (MT-DTE) as compared to baseline. However, these early time points did not correlate with clinical response. We observed that the CTCs collected one week after the first or second dose of CRXL301 treatment in the responding patient had numerically higher levels of MT-DTE as compared to the other two patients.
conclusionTaxane on-target activity can be detected and analyzed quantitatively in CTCs by tubulin immunofluorescence. Early time points, within 24 h of drug administration, showed high levels of DTE but did not correlate with clinical response. MT-DTE in CTCs collected after one week on treatment correlated best with treatment response. The clinical utility of the 1-week CTC DTE should be tested and validated in future clinical trials involving taxanes.
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