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 nano-sized 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.
Molecular cancer therapeutics. 2017 Jul 20 [Epub ahead of print]
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
Department of Physiology and Pharmacology, Tel Aviv University., Pediatric Stem Cell Research Institute, Sheba Medical Center., Department of Pathology, Sheba Medical Center., Department of Physiology and Pharmacology, Tel Aviv University .