Unlocking the potential: Targeting metabolic pathways in the tumor microenvironment for Cancer therapy.

Cancer incidence and mortality are increasing and impacting global life expectancy. Metabolic reprogramming in the tumor microenvironment (TME) is intimately related to tumorigenesis, progression, metastasis and drug resistance. Tumor cells drive metabolic reprogramming of other cells in the TME through metabolic induction of cytokines and metabolites, and metabolic substrate competition. Consequently, this boosts tumor cell growth by providing metabolic support and facilitating immunosuppression and angiogenesis. The metabolic interplay in the TME presents potential therapeutic targets. Here, we focus on the metabolic reprogramming of four principal cell subsets in the TME: CAFs, TAMs, TILs and TECs, and their interaction with tumor cells. We also summarize medications and therapies targeting these cells' metabolic pathways, particularly in the context of immune checkpoint blockade therapy.

The role of novel protein acylations in cancer.

Novel protein acylations are a class of protein post-translational modifications, such as lactylation, succinylation, crotonylation, palmitoylation, and ß-hydroxybutyrylation. These acylation modifications are common in prokaryotes and eukaryotes and play pivotal roles in various key cellular processes by regulating gene transcription, protein subcellular localization, stability and activity, protein-protein interactions, and protein-DNA interactions. The diversified acylations are closely associated with various human diseases, especially cancer. In this review, we provide an overview of the distinctive characteristics, effects, and regulatory factors of novel protein acylations. We also explore the various mechanisms through which novel protein acylations are involved in the occurrence and progression of cancer. Furthermore, we discuss the development of anti-cancer drugs targeting novel acylations, offering promising avenues for cancer treatment.

The role of circadian gene CLOCK in cancer.

Circadian Locomotor Output Cycles Kaput (CLOCK) is one of the circadian clock genes and is considered to be a fundamental regulatory gene in the circadian rhythm, responsible for mediating several biological processes. Therefore, abnormal expression of CLOCK affects its role in the circadian clock and its more general function as a direct regulator of gene expression. This dysfunction can lead to severe pathological effects, including cancer. To better understand the role of CLOCK in cancer, we compiled this review to describe the biological function of CLOCK, and especially highlighted its function in cancer development, progression, tumor microenvironment, cancer cell metabolism, and drug resistance.

CYLD induces high oxidative stress and DNA damage through class I HDACs to promote radiosensitivity in nasopharyngeal carcinoma.

Abnormal expression of Cylindromatosis (CYLD), a tumor suppressor molecule, plays an important role in tumor development and treatment. In this work, we found that CYLD binds to class I histone deacetylases (HDAC1 and HDAC2) through its N-terminal domain and inhibits HDAC1 activity. RNA sequencing showed that CYLD-HDAC axis regulates cellular antioxidant response via Nrf2 and its target genes. Then we revealed a mechanism that class I HDACs mediate redox abnormalities in CYLD low-expressing tumors. HDACs are central players in the DNA damage signaling. We further confirmed that CYLD regulates radiation-induced DNA damage and repair response through inhibiting class I HDACs. Furthermore, CYLD mediates nasopharyngeal carcinoma cell radiosensitivity through class I HDACs. Thus, we identified the function of the CYLD-HDAC axis in radiotherapy and blocking HDACs by Chidamide can increase the sensitivity of cancer cells and tumors to radiation therapy both in vitro and in vivo. In addition, ChIP and luciferase reporter assays revealed that CYLD could be transcriptionally regulated by zinc finger protein 202 (ZNF202). Our findings offer novel insight into the function of CYLD in tumor and uncover important roles for CYLD-HDAC axis in radiosensitivity, which provide new molecular target and therapeutic strategy for tumor radiotherapy.