TRIAL-based combination therapies in cancers.

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) shows promising therapeutic potential in cancer treatment as it is able to trigger extrinsic apoptotic pathways by binding to the cognate death receptor, causing broad-spectrum apoptosis in cancer cells with negligible toxicity to normal cells. However, the majority of cancers display resistance to TRAIL, limiting its clinical utility. Overcoming resistance to TRAIL therapies remains a challenge in the development of effective anti-cancer strategies.

Methylation of promoter induced by SNAI2-DNMT3B complex promotes epithelial-mesenchymal transition and correlates with poor prognosis in ERα-positive breast cancers.

Estrogen receptor α (ERα) serves as an essential therapeutic predictor for breast cancer (BC) patients and is regulated by epigenetic modification. Abnormal methylation of cytosine phosphoric acid guanine islands in the estrogen receptor 1 (ESR1) gene promoter could silence or decrease ERα expression. In ERα-negative BC, we previously found snail family transcriptional repressor 2 (SNAI2), a zinc-finger transcriptional factor, recruited lysine-specific demethylase 1 to the promoter to transcriptionally suppress ERα expression by demethylating histone H3 lysine 4 dimethylation (H3K4me2).

TOPK/PBK is phosphorylated by ERK2 at serine 32, promotes tumorigenesis and is involved in sorafenib resistance in RCC.

TOPK/PBK (T-LAK Cell-Originated Protein Kinase) is a serine/threonine kinase that is highly expressed in a variety of human tumors and is associated with poor prognosis in many types of human malignancies. Its activation mechanism is not yet fully understood. A bidirectional signal transduced between TOPK and ERK2 (extracellular signal-regulated kinase 2) has been reported, with ERK2 able to phosphorylate TOPK at the Thr9 residue.