Table 1.
The alternative strategies for targeting SOX factors in cancers.
| Strategy | Target | Biomarker | Cancer | Mechanism of Action | Clinical Trial |
|---|---|---|---|---|---|
| SOX factors as biomarkers for patient stratification treatment | |||||
| MRT-92 plus MZ1 [162] |
SMO+ BRD4 |
SOX2 | Melanoma | SMO and SOX2-BRD4 complex activate hedgehog/GLI signaling in canonical and noncanonical manners, respectively | / |
| Integrin αvβ6/8 mAb [151] | Integrin αvβ6/8 | SOX4 | TNBC | Integrin αv up-regulates SOX4 by activating TGFβ from a latent precursor | Phase II NCT03688230 |
| LGK974 [163] |
WNT | SOX9 | Prostate cancer | SOX9 reactivates the WNT/β-catenin signaling | Phase I NCT01351103 |
| Rapamycin [164] |
mTOR | SOX9 | Esophageal cancer | SOX9 inhibits miR-203a to activate the PI3K/AKT/mTOR signaling | Phase III NCT04736589 |
| BLU9931 [134] |
FGFR4 | SOX18 | HCC | SOX18 transactivates FGFR4 and FLT4, and FGFR4-FGF19 in turn up-regulates SOX18 | / |
| Targeting SOX proteins degradation | |||||
| SAHA [145] |
SOX2 | SOX2 | Melanoma | Promoting SOX2 acetylation and proteasome-dependent degradation | Phase I/II NCT02638090 |
| ChlA-F [165] |
SOX2 | SOX2 | Bladder cancer | promoting SOX2 ubiquitination and protein degradation by enhancing the mRNA stability of USP8 and inhibiting SOX2 protein translation by activating c-Jun-miR-200c | / |
| SOX factors as peptide vaccine boost anti-tumor immune response | |||||
| SOX2-derived peptide [166] |
SOX2 | SOX2 | Glioblastoma | As a tumor-specific vaccine antigen to augment CTLs response | Phase I NCT02157051 |
| SOX4-derived peptide [167] |
SOX4 | SOX4 | Lung cancer | As a tumor-specific vaccine antigen to augment CTLs response | / |
| SOX6-derived peptide [168,169] |
SOX6 | SOX6 | Glioblastoma | As a tumor-specific vaccine antigen to augment CTLs response | / |
| SOX11-derived peptide [170] |
SOX11 | SOX11 | Glioblastoma | As a tumor-specific vaccine antigen to augment CTLs response | / |
| Tumor-targeted delivery of siRNA to silence SOX expression | |||||
| CL-siSOX2 [171] |
SOX2 | SOX2 | Lung cancer | Deliver therapeutic siRNA targeting SOX2 to tumor in vivo through a lipoplex nanoparticle | / |
| RGDfC-SeNPs-siSOX2 [172] |
SOX2 | SOX2 | HCC | Deliver therapeutic siRNA targeting SOX2 to tumor in vivo through a RGDfC-SeNP system | / |
| Targeting endogenous SOX expression by artificial transcription factors-based technologies | |||||
| ZF-552SKD [173] |
SOX2 promoter | SOX2 | Breast cancer | ZF-based ATF inhibits SOX2 expression through recruiting transcriptional repressor SKD domain to the SOX2 promoter and recruiting co-repressor KAP1 to facilitate chromatin condensation | / |
| ZF-598SKD [173] |
SOX2 promoter | SOX2 | Breast cancer | ZF-based ATF inhibits SOX2 expression through recruiting transcriptional repressor SKD domain to the SOX2 promoter and recruiting co-repressor KAP1 to facilitate chromatin condensation | / |
| ZF-619SKD [173] |
SOX2 promoter | SOX2 | Breast cancer | ZF-based ATF inhibits SOX2 expression through recruiting transcriptional repressor SKD domain to the SOX2 promoter and recruiting co-repressor KAP1 to facilitate chromatin condensation | / |
| ZF-4203SKD [173] |
SOX2 regulatory region I | SOX2 | Breast cancer | ZF-based ATF inhibits SOX2 expression through recruiting transcriptional repressor SKD domain to the SOX2 promoter and recruiting co-repressor KAP1 to facilitate chromatin condensation | / |
| ATF/SOX2 [174] |
SOX2 promoter | SOX2 | Lung and esophageal SCC | ZF-based ATF inhibits SOX2 expression through targeting the SOX2 distal and proximal promoter region and a KOX transcriptional repressor domain | / |
Abbreviations: SMO: Smoothened; SOX: Sex-determining region Y-related high-mobility group box; mAb: Monoclonal antibody; TNBC: Triple-negative breast cancer; HCC: Hepatocellular carcinoma; SAHA: Suberoylanilide hydroxamic acid; CTLs: Cytotoxic T lymphocytes; CL-siSOX2: siSOX2 delivered by cationic lipoplex; RGDfC-SeNP: RGDfC-modified functionalized selenium nanoparticles; ZF-based ATF: Zinc-finger-based Artificial transcription factors; SKD: Kruppel Associated box; SCC: Squamous cell carcinoma;.