Signaling pathways as the pivotal regulators of cisplatin resistance in tumor cells through SOX2 upregulation.

Chemotherapy is one of the first-line treatment options in cancer patients. Cisplatin (CDDP) is widely used as one of the antineoplastic agents in many cancers. Nevertheless, CDDP resistance is considered as a therapeutic challenge in cancer. Considering the CDDP side effects in normal tissues, prediction of CDDP response helps to select a suitable therapeutic strategy in cancer patients. Sex-determining region Y-box 2 (SOX2) is a critical regulator of tumor growth and embryogenesis that is involved in tumor metastasis, apoptosis, and cell proliferation, through association with other developmental/oncogenic signaling pathways. SOX2 has also a crucial role in CDDP resistance in tumor cells. Therefore, we discussed the role of SOX2 in regulation of CDDP response in tumor cells. It has been reported that SOX2 upregulation through PI3K/AKT, WNT, Hippo, and TGF-β signaling pathways mainly promotes the CDDP resistance in tumor cells. The present review can be an effective step in introducing SOX2 as a prognostic marker as well as a therapeutic target in cancer patients.