4sc‐202 and Ink‐128 cooperate to reverse the epithelial to mesenchymal transition in OSCC

Abstract

Oral squamous cell carcinoma (OSCC) is the most common malignancy of the head and neck mucosa, and over 300,000 new cases are reported each year. Currently, the main treatment modalities for OSCC include surgical resection combined with radiochemotherapy (Siegel, 2018). Unfortunately, the 5-year survival rates for patients with OSCC have remained less than 50% due to the high incidence of treatment resistance, with subsequent tumor recrudescence and metastasis to the lymph nodes (Ali et al., 2017). Therefore, the development of novel, effective therapeutic approaches for overcoming treatment resistance and metastasis has become a primary objective.Gene expression profiling and other methods have identified gene expression changes related to the epithelial-mesenchymal transition (EMT) as significant factors in the development and/or progression of OSCC (Kurth et al., 2015). The EMT is a strictly regulated process during cancer progression, whereby epithelial cells lose their polarity and cell-cell adhesion, and acquire capabilities for

Reduction of Metastasis via Epigenetic Modulation in a Murine Model of Metastatic Triple Negative Breast Cancer (TNBC)

“…Other studies have also demonstrated that 4SC-202 reduces cell viability, induces apoptosis and causes G2/M cell cycle arrest in a wide variety of conditions, including myelodysplastic syndrome (MDS) [ 30 ], urothelial carcinoma [ 6 , 31 ], and colorectal cancer [ 5 ]. In addition, other studies have demonstrated reduced migration and invasion in vivo in oral squamous cell carcinoma (OSCC) [ 32 ], as well as a wide variety of different cancer cell lines, including urothelial carcinoma [ 6 ], colorectal cancer cells [ 5 ] and highly aggressive pancreatic cancer [ 8 ]. On the clinical side, studies have demonstrated administration of 4SC-202 was safe and well tolerated with potential antitumor activity such as in hematological malignancies [ 33 ].…”

Targeting histone deacetylases in head and neck squamous cell carcinoma: molecular mechanisms and therapeutic targets

“…This combination also decreased OSCC invasion and migration by inhibiting TWIST1 expression and STAT3 phosphorylation [172]. Combining 4SC-202 and mTOR inhibitor Ink-128 reduced EMT in OSCC cells by activating FoxO1 and inhibiting Twist1 [173]. Moreover, the combined administration of 4SC-202 and INK128, a specific mTORC1/C2 inhibitor, induced the reduction of SOX2 expression via miR-429/miR-1181 mediated mRNA degradation and inhibition of cap-dependent mRNA translation.…”