Wilms tumor NCAM-expressing cancer stem cells as potential therapeutic target for polymeric nanomedicine

Ela Markovsky, Einav Vax, Dikla Ben-Shushan, Anat Eldar-Boock, Rachel Shukrun, Eilam Yeini, Iris Barshack, Revital Caspi, Orit Harari-Steinberg, Naomi Pode-Shakked, Benjamin Dekel, Ronit Satchi-Fainaro

Research output: Contribution to journalArticlepeer-review

Abstract

Cancer stem cells (CSC) form a specific population within the tumor that has been shown to have self-renewal and differentiation properties, increased ability to migrate and form metastases, and increased resistance to chemotherapy. Consequently, even a small number of cells remaining after therapy can repopulate the tumor and cause recurrence of the disease. CSCs in Wilms tumor, a pediatric renal cancer, were previously shown to be characterized by neural cell adhesion molecule (NCAM) expression. Therefore, NCAM provides a specific biomarker through which the CSC population in this tumor can be targeted. We have recently developed an NCAM-targeted nanosized conjugate of paclitaxel bound to a biodegradable polyglutamic acid polymer. In this work, we examined the ability of the conjugate to inhibit Wilms tumor by targeting the NCAM-expressing CSCs. Results show that the conjugate selectively depleted the CSC population of the tumors and effectively inhibited tumor growth without causing toxicity. We propose that the NCAM-targeted conjugate could be an effective therapeutic for Wilms tumor.

Original languageEnglish
Pages (from-to)2462-2472
Number of pages11
JournalMolecular Cancer Therapeutics
Volume16
Issue number11
DOIs
StatePublished - Nov 2017

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