Targeting SOX2 in anticancer therapy

ABSTRACT

Introduction: SOX2 is a transcription factor that is important in the development and maintenance of the stem cell state. Furthermore, SOX2 is associated with cancer progression because it promotes the migration, invasion, and proliferation of cancer cells. SOX2 is also expressed in cancer stem cells and appears to be involved in the resistance toward anticancer therapies. These features render SOX2 an attractive target for cancer therapy.

Areas covered: In this review, we highlight the role of SOX2 in cancer and in the resistance toward anticancer therapies. We summarize recent studies dealing with SOX2 as a direct or indirect therapeutic target in cancer.

Expert opinion: SOX2 is an attractive target in cancer therapy because of its role in cancer progression and therapy resistance. SOX2 is a transcription factor, hence direct targeting is difficult. Studies aimed at a functional depletion, for example by knock-down with siRNAs, are difficult to translate into clinical settings. Alternatively, the identification of SOX2 upstream or downstream regulators that are easier to target is of paramount importance.

KEYWORDS:

• Cancer
• SOX2
• therapeutic targets
• therapy resistance
• resistance
• tumor

Article Highlights

• SOX2 is involved in cancer progression by promoting cancer cell survival, invasion, migration, proliferation, and colony and sphere formation, and by preventing apoptosis

• SOX2 is a transcription factor, which is important for the maintenance of stem cell features of tumor cells since it is involved in the maintenance of pluripotency

• SOX2 was shown to be involved in cancer cell resistance toward different cancer therapies like chemotherapy, radiotherapy, and targeted therapy

• SOX2 was suggested as a target for cancer therapy due to its important role in cancer progression as well as therapy resistance

• Various studies show that SOX2 can be targeted directly or indirectly by different approaches to prevent cancer cell progression and resistance toward other therapies

This box summarizes key points contained in the article.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported by the German Research Council Research Training Group (RTG) 2099 Hallmarks of Skin Cancer.