PCLAF (PCNA Clamp Associated Factor)

Future efforts must prioritize functional validation of novel targets (DKK2, ELF3), spatial multi-omics to resolve CAF-immune-metabolic crosstalk, and biomarker-driven clinical trials integrating single-cell classifiers. By bridging single-cell insights with mechanistic and translational studies, the field can overcome stromal-mediated resistance and usher in an era of precision immunotherapy for CC.

Notably, risperidone (SM-2) emerged as a potential inhibitory regulator capable of disrupting the cascade effects mediated by the GDF15-GFRAL axis, underscoring its therapeutic relevance. This study identifies the GDF15-GFRAL signaling axis as a critical regulator of oxidative stress and immune evasion in HNSCC and demonstrates that the novel small-molecule SM-2 effectively targets this pathway, highlighting its potential as a promising therapeutic strategy.

In patient-derived xenograft (PDX) models, combined therapy of clathrin inhibitor (chlorpromazine) or SH3KBP1 silencing with sorafenib suppresses tumor growth and reduces microvascular density. This study demonstrates that CLTB promotes HCC progression through the NF-κB-PCLAF signaling axis and sEV-mediated vascular remodeling, providing a mechanistic foundation for developing combination therapies targeting CLTB.

YEATS4 knockdown effectively suppressed malignant tumor behaviors, highlighting its therapeutic potential. These findings provided novel targeted intervention strategies to address GBM heterogeneity and treatment resistance, offering promising avenues for overcoming current therapeutic limitations.

The expression of KIAA0101 gene also shows a significant increase in the tissues collected from 31 patients with tumor. Inhibition of KIAA0101 expression can regulate cell proliferation and apoptosis in colorectal cancer.

Mitotane, the medication licenced for ACC, has had mixed results...Paclitaxel and cisplatin were the central nodes within the drug-gene network...Network analysis shows fluorouracil and epirubicin target the ACC novel hub gene, HMMR. Fluorouracil was more effective due to its impact on M2 macrophage infiltration.

Spatial transcriptomics revealed a correlation between the distribution of SPHK1 and M2-like macrophage. By integrating multi-omics data and further cellular experiments, we propose that inhibition of S1P may play an important role in inhibiting angiogenesis and reversing M2-type macrophage polarization, demonstrating its anti-tumor efficacy in CRC.

Also, drug screening identified potential therapeutic agents targeting these hub genes.The findings increase mechanistic understanding with potential clinical applications. Future validation studies that include multi-omic data may strengthen current hypotheses and enable targeted therapy design against crucial in HCC.

In colon cancer animal models, X21 exerted in vivo anti-tumor efficacy, probably through synergistic effects of direct cytotoxicity and immune microenvironment improvement. These findings may provide directions for future design of novel USP7 inhibitors and facilitate the exploration of new mechanism of USP7 inhibitors.

In conclusion, our findings suggest that silencing PCLAF hinders EC progression by suppressing the Wnt/β-catenin pathway and activating the p53 signaling pathway. This insight suggested that targeting PCLAF may offer a new therapeutic avenue for EC treatment.

The model containing CNR1, PRKACB, CDKN3, and PCLAF can serve as a new prognostic biomarker for predicting the prognosis of patients with neuroblastoma. Findings on immune cell infiltration and immune checkpoints provide novel insights for the immunotherapy of neuroblastoma.

Our findings illuminate the heterogeneity of the complex TME in CSCC and offer evidence supporting PCLAF+ TAEpis as a promising therapeutic target.