Two cancer stem cell-targeted therapies in clinical trials as viewed from the standpoint of the cancer stem cell model

Abstract

A key implication of the cancer stem cell model is that for a cancer therapy to be curative, it is imperative to eliminate the cancer stem cells (CSCs) that drive tumor progression. The California Institute for Regenerative Medicine is supporting two novel approaches that target CSCs, one an antibody‐mediated immunotherapy targeting CD47 and the other an antibody targeting ROR1. This article summarizes the evidence that CSCs are targeted and discusses the results of early clinical trials within the context of the CSC model.

Patient-Derived Tumor Chemosensitization of GKB202, an Antrodia Cinnamomea Mycelium-Derived Bioactive Compound

“…A purified derivative of maleic and succinic acid, YMGKI-1, was previously discovered in those ACM ethanolic extracts which have shown inhibition in the stemness of head and neck cancer initiating cells both in vitro and in vivo [ 12 ]. Despite the increasing evidence that AC has the capability to diminish the stemness of cancer initiating cells through modulating tumor miRNA expressions [ 13 , 14 , 15 ], there are still great challenges to translate in vivo findings into current human clinical trials endpoints [ 16 ].…”

Cancer Stem Cells: Future Possibilities for Cancer Therapy

“…The second clinical trial employs anti-ROR1, a receptor for Wnt5a signalling that has been linked to CSC maintenance, self-renewal, and metastasis. Anti-ROR1 antibody (cirmtuzumab) that suppresses ROR1-dependent Wnt5a signalling has also demonstrated encouraging benefits in this experiment [7].…”

Targeting cancer stem cell plasticity in triple-negative breast cancer

“…The TKI inhibitor dasatinib has shown efficacy in targeting CSCs in TNBC by blocking CSC enrichment and Src activation, inducing EMT, and enhancing sensitivity to paclitaxel [131]. Similarly, mAbs targeting the CSC markers CD47 or ROR1 have shown efficacy against TNBC in preclinical models [132][133][134]. Antibody-drug conjugates (ADCs) are a novel strategy for targeting CSCs in TNBC, which consists of an antibody that targets a specific antigen on the surface of cancer cells, linked to a cytotoxic drug that kills the targeted cells.…”