Targeting SOX2 in anticancer therapy

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“…In our publication [5] we could demonstrate that the initial STAT3 activation induced by BRAF inhibitor treatment resulted in an increased expression of SOX2 and CD24 which were both associated to an increased resistance since overexpression of either SOX2 or CD24 resulted in a significantly higher tolerance against BRAF inhibitors. In contrast, the knock down of both molecules rendered cells more sensitive towards the treatment.SOX2 was demonstrated before to be a cancer stem cell marker and its expression is increased in melanospheres which showed a higher resistance towards the BRAF inhibitor vemurafenib [6,7]. Interestingly, we could show that SOX2 is able to bind to the CD24 promotor and thereby promoting the CD24 expression.…”

Targeting oncogenic SOX2 in human cancer cells: therapeutic application

“…Furthermore, SOX2 is causally related to the development of the resistance of cancer cells to chemotherapy, radiotherapy and targeted therapy in different types of human cancers, likely due to its ability to maintain the stemness of cancer stem cells (CSCs), which are defined as a subpopulation within tumor cells being equipped with stem cell-like properties that survives the treatment and initiates tumor progression (Novak et al, 2019). Thus, SOX2 has been validated as an attractive anticancer target (Huser et al, 2018).…”

“…Although SOX2 is highly relevant to cancer initiation, progression and development of drug resistance, directly targeting SOX2 has been proved to be difficult, since SOX2 is an "undrugable" transcription factor. The multiple preclinical studies have shown that SOX2 knockdown mediated by siRNAs, shRNAs or miRNAs dramatically suppresses proliferation and invasion of cancer cells in both in vitro cell culture and in vivo xenograft tumor models (Huser et al, 2018). These studies validate SOX2 as a promising target, but offer little therapeutic value due to huge challenge in efficacy and delivery.…”

“…On the other hand, zinc-finger (ZF)based artificial transcription factors (ATFs), which bind genomic sequences with potentially single locus specificity, provide an opportunity to modify, edit, and sculpt the epigenetic and transcriptional state of endogenous promoters. Indeed, ATFs that bind to the proximal SOX2 promoters were shown to cause ∼95% reduction of endogenous SOX2 mRNA and protein in breast cancer cells upon retrovirus-based delivery (Huser et al, 2018). Significantly, these ATFs efficiently inhibited tumor growth in a xenograft model of breast cancer with the inhibitory effect maintained for a long term (Huser et al, 2018).…”

“…Indeed, ATFs that bind to the proximal SOX2 promoters were shown to cause ∼95% reduction of endogenous SOX2 mRNA and protein in breast cancer cells upon retrovirus-based delivery (Huser et al, 2018). Significantly, these ATFs efficiently inhibited tumor growth in a xenograft model of breast cancer with the inhibitory effect maintained for a long term (Huser et al, 2018). Again, the challenge in the in vivo delivery of ATFs to solid tumor tissues constrains the clinical applications.…”