In summary, base editor screen provides a versatile approach for exploring the role of phosphorylation sites in cancer chemotherapy. The METTL3-eIF3H interaction may serve as a potential therapeutic target.

Here, we report that the pro-inflammatory disulfide isoform of high-mobility group box 1 (ds-HMGB1) is a key mediator of oxaliplatin-induced neuropathic pain, with DRG microglia-like tissue-resident macrophages (M-TRMφs) as its primary reservoir...M-TRMφ-derived ds-HMGB1 orchestrates neuropathic pain through pyroptotic release and TLR4/TRPV1 signaling in a redox-regulated macrophage-neuron axis in the DRG. ds-HMGB1 emerges as a potential biomarker and therapeutic target in CIPN.

Neoadjuvant chemotherapy prior to laparoscopic radical resection for rectal cancer was associated with improved anus preservation, enhanced postoperative recovery, and greater biochemical and functional benefits without increasing major complication rates, although it was linked to higher hematologic adverse events and postoperative declines in immune cell counts.

Treatment with gemcitabine and oxaliplatin chemotherapy showed significant improvement, complemented by radiotherapy for refractory lesions. Histopathological evaluation and EBV testing are critical for differentiation from other conditions. While initial responses to chemoradiotherapy are promising, recurrence remains common, highlighting the need for vigilant follow-up and optimized therapeutic strategies.

The LNMRGS is a robust prognostic signature for CRC. NPR3 plays a key role in metastatic progression and chemoresistance, suggesting it as a potential therapeutic target.

The rare genetic co-occurrence of t(15;17)/PML::RARA and t(9;22)/BCR::ABL1 translocations may be identified in a single patient with acute promyelocytic leukaemia (APL).Successful induction using all-trans retinoic acid (ATRA) together with imatinib achieved effective control of both leukemic clones.The patient demonstrated rapid haematologic remission and favourable clinical recovery, suggesting a positive outcome with this therapeutic approach.

Diagnosis requires systematically excluding other primary squamous cell carcinoma sites (oesophagus, lung, head and neck) before confirming primary gastric squamous cell carcinoma (GSCC).Radical resection (R0) combined with aggressive adjuvant chemotherapy is the optimal treatment strategy, offering the best survival chance even in advanced disease (pT4bN3aM0, LVI+/PNI+).Treatment must be individualised due to a lack of standardised protocols: for this extremely rare malignancy, the decision between upfront surgery versus neoadjuvant chemotherapy should be based on tumour resect ability, biological characteristics and multidisciplinary tumour board discussion.

The GEMSTONE-303 trial demonstrated that sugemalimab combined with capecitabine and oxaliplatin (CAPOX) improved survival benefit in patients with advanced gastric/gastroesophageal junction cancer (GC/GEJC) and a programmed death-ligand 1 (PD-L1) combined positive score (CPS) ≥5. It is essential to adopt a combination of targeted patient selection, price negotiation, and broader PAP access to bring the ICER below the WTP threshold. These findings inform reimbursement negotiations and highlight the need for stratified pricing strategies to optimize accessibility in economically diverse populations.

Importantly, these events interacted with cholesterol metabolic regulation to form a self-amplifying cycle, which substantially enhanced damage-associated molecular pattern release to strengthen ICD and further modulated the TME by promoting CD8+ T cell infiltration and cytokine secretion while downregulating PD-L1 expression and Treg-mediated immunosuppression. In vivo, these conjugates exhibited favorable biocompatibility, potent antitumor activity and reduced toxicity compared to oxaliplatin.

Nonetheless, these metabolic increases also generate reactive oxygen species (ROS), inducing DNA damage and significantly enhancing colorectal cancer cell sensitivity to oxaliplatin. The latter provides an explanation as to why colorectal tumors with high ACSL5 expression display preferentially improved patient outcomes from chemotherapy. Collectively, the findings reveal a new pathway for non-genetic chemotherapy resistance mechanisms, deepen the understanding of metabolic reprogramming in tumor cells, and offer potential therapeutic targets for future treatment strategies.

Therapeutic targeting of this axis with the EGFR inhibitor gefitinib restored oxaliplatin sensitivity in vitro and synergistically suppressed RBM8A-driven xenograft growth in vivo. Additionally, single-cell RNA-seq revealed RBM8A enrichment in malignant gastric epithelial cells, while tissue microarrays confirmed that dual RBM8A/EGFR overexpression predicts the poorest survival outcomes. Collectively, our findings define the RBM8A-eIF4A3-EGFR axis as a druggable determinant of chemoresistance and establish RBM8A as both a prognostic biomarker and therapeutic target in GC.