PDX1 (Pancreatic And Duodenal Homeobox 1)

This predisposes to genomic instability and pancreatic preneoplastic lesion development. These findings uncover a metabolic-epigenetic axis in dysmetabolic PDAC, highlighting how metabolite-driven epigenetic changes compromise DNA repair and drive tumorigenesis.

Levels of inter-alpha-trypsin inhibitor heavy chain H3 (ITIH3) were significantly elevated in all three screens, with complement C5, complement factors B and H (CFB/CFH), and monocyte differentiation antigen CD14 increased in KPC mice and PDAC patients; and all were significantly increased co-ordinately in PDAC according to disease stage. Serum levels of C5, CFH and CD14 together constitute a novel panel for identifying PanINs and early-stage PDAC with confidence, and when combined with additional screening, could help increase survival from this dismal disease.

PDIA6, driven by KRASG12D, alleviates ICD and promotes immune evasion, functioning as a predictive biomarker to screen ICB-sensitive patients and a therapeutic target to improve ICB efficacy in PDAC with KRAS mutations.

Collectively, our findings reveal that the USP20-RAB8A-GLUT1 axis regulates glucose uptake and metabolic reprogramming in PDAC, thereby inhibiting tumor growth and metastasis. Targeting this signaling axis provides a novel insight into metabolic therapy for pancreatic cancer.

In contrast, the expression of CD4, CD8, CD31, and CD34 was significantly reduced in PDX0 and PDX1 tumors compared with PTT. OSCC PDX tumors may exhibit instability in the degree of differentiation compared with the donor tumors across passages, as well as alterations in certain components of the TME, including cancer-associated fibroblasts, epithelial-mesenchymal transition-related features, and cellular proliferation characteristics.

In 3D co-cultured human spheroid models, the peptide decreased markers of resistance (ABCG1, BCL2, CXCR4), stemness (WNT1, CD44) and ECM remodeling (COL1A1, MMP2/9, LOX) and enhanced gemcitabine efficacy...These effects were attributed to reduced desmoplasia, vasculature compression and enhanced infiltration of cytotoxic T cells and apoptosis. This study presents a novel cyclic peptide inhibiting ITGA5-mediated tumor-stroma interaction and thereby reduce desmoplasia and resistance, ultimately enhancing chemotherapy efficacy in PDAC.

Given the dual role of PDX1 in tumorigenesis, its aberrant expression offers potential applications in tumor diagnosis, treatment, and prognosis. The present review explored the structure, function, and mechanisms of PDX1 in tumors, as well as its clinical translational potential, aiming to provide insights for further basic research and pave the way for clinical drug development.

Anti-mouse CLDN18.2 CAR-T cells suppressed tumor growth of mice bearing the syngeneic graft of S6M but not the CLDN18.2-low S1M cell line. Dual inhibition of immunosuppressive molecules TGF-β and PD-L1 enhanced the in vivo efficacy of anti-mouse CLDN18.2 CAR-T against S6M cells by recruiting NK cells to tumor microenvironment, suggesting the potential utility of our novel syngeneic gastric cancer cell line model in designing innovative clinical therapeutic approaches.

Consistent with the human data, experiments in zebrafish showed that TNFRSF1A expression increases significantly following pdx1 knockdown (p = 0.0025). Together, these findings support a role for TNFRSF1A in immune microenvironment reprogramming in DKD, while not excluding the involvement of additional regulatory pathways.

KRAS mutations and hyperglycaemia drive O-GlcNAcylation of CLDN18.2 at its C-terminal T204 site. O-GlcNAcylated CLDN18.2 promotes poor prognosis and reduces the effectiveness of CLDN18.2-targeted therapies. Low dose MRTX1133 restores CLDN18.2 membrane localisation by reducing its O-GlcNAcylation and augments CLDN18.2-targeted therapy efficacy, offering a novel combinatorial strategy for KRAS-mutant PDAC.

These data suggest that the netrin-1/NEO1 axis is a key regulator of PDAC progression, directly influencing cancer cell stemness and EMT, while indirectly promoting tumor growth through nerves. Inhibiting the netrin-1 pathway could represent a potential therapeutic approach for PDAC.

This review delves into the various functions of RFX6, emphasizing its crucial regulatory roles in pancreatic development, tumorigenesis, and progression. In addition, recent advancements in MRS therapy are outlined, underscoring the importance of RFX6-targeted therapy in MRS and cancer.