The antigen CD44 is expressed on the surface of pancreatic cancer stem cells (PCSCs) and modulates the cytoskeleton via the linker protein ezrin, which is more active and present in higher levels in these stem cells than in differentiated tumor cells (Penchev et al. 2019). Elimination of ezrin as well as targeting via a small molecule inhibitor has been found to decrease self-renewal, clonogenic growth, and migration in vitro as well as tumor initiation in vivo (Penchev et al. 2019). Natural compounds and phytochemicals such as curcumin, resveratrol, tea polyphenol EGCG (epigallocatechin-3-gallate), crocetinic acid, sulforaphane, genistein, indole-3-carbinol, vitamin E δ-tocotrienol, plumbagin, quercetin, triptolide, licofelene, and quinomycin have also been shown to inhibit PCSCs as well as their signaling pathways (Subramaniam et al. 2018). These treatments to inhibit self-renewal may be useful in phase 1 of our treatment plan, but a method to induce differentiation back into pancreatic cancer cells has yet to be researched. The premetastatic niche may also be able to be targeted in phase 1 of treatment, but effective targets have yet to be researched as well.
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