Imbalanced p53-RB signaling triggers cGAS-STING-mediated immune activation in early oral cancer development.

NTMT1 (METTL11A) promotes MYC-dependent proliferation and downstream HLA-A suppression in cervical cancer

Findings identify NTMT1 as a candidate regulatory node associated with MYC activation and downstream HLA-A suppression, warranting further mechanistic and in-vivo investigation, and highlighting NTMT1 as a promising candidate for future therapeutic investigation.

A CD109-SMURF2 Axis Diverts EGFR from Degradation to Sustain Oncogenic Signaling and Promote Squamous Cell Carcinoma Invasion and Stemness

TLSB-09 TARGETED P16 KNOCKOUT CONFERS AN IMMUNOSUPPRESSIVE MICROENVIRONMENT IN PRECLINICAL MODELS OF TRIPLE NEGATIVE BREAST CANCER BRAIN METASTASIS

A role for p16 loss as a candidate functional driver of ICI resistance associated with 9p21 loss in TNBC-BM is suggested and warrant further investigation given the need to nominate biomarkers for ICI response to inform patient care.

p53 hotspot mutants attenuate CTL-mediated tumor cell killing through a novel ALKBH5-YTHDF3-PD-L1 pathway

ZC3H13‐mediated m6A stabilization of CCND1 promotes malignant progression and is associated with poor anti‐PD‐1 response in HNSCC

Abstract Background Resistance to immune checkpoint blockade substantially limits its clinical efficacy in head and neck squamous cell carcinoma(HNSCC). ZC3H13 is a component of the N6‐methyladenosine writer complex, but its roles in HNSCC progression and response to anti‐programmed cell death protein 1(anti‐PD‐1) therapy remain unclear. Methods The expression and clinical relevance of ZC3H13 were evaluated using clinical cohorts and publicly available transcriptomic datasets. Gain‐ and loss‐of‐function experiments were performed to determine the effects of ZC3H13 on the malignant phenotypes of HNSCC cells. An epithelial‐specific ZC3H13 conditional knockout mouse model of 4‐nitroquinoline‐1‐oxide‐induced oral tumorigenesis was used to assess tumor development and responsiveness to anti‐PD‐1 therapy. N6‐methyladenosine modification, RNA stability and functional rescue assays were conducted to investigate the underlying molecular mechanism. Results ZC3H13 was upregulated in HNSCC and was associated with poor prognosis and a limited response to anti‐PD‐1 treatment. ZC3H13 promoted the proliferation and invasion of HNSCC cells, whereas epithelial‐specific ablation of ZC3H13 suppressed oral tumorigenesis and enhanced the therapeutic efficacy of anti‐PD‐1 treatment. Mechanistically, ZC3H13 regulated the N6‐methyladenosine modification of cyclin D1(CCND1) mRNA and promoted its IGF2BP1‐dependent stabilization, thereby contributing to malignant tumor phenotypes and alterations in immunosuppressvie features. Conclusions The ZC3H13/IGF2BP1/CCND1 regulatory axis contributes to HNSCC progression and resistance to anti‐PD‐1 therapy. These findings identify ZC3H13 as a potential therapeutic target for improving the efficacy of anti‐PD‐1 treatment in HNSCC.

ZBTB33/RBM15 Axis Upregulates MACC1 to Promote the Malignant Progression of Colorectal Cancer.

Clinically, these findings not only deepen the understanding of m6A-mediated posttranscriptional regulation in CRC but also identify this axis as a promising therapeutic target for overcoming ferroptosis resistance and improving patient outcomes.