Background Chemotherapy resistance is a primary reason of ovarian cancer therapy failure; hence it is important to investigate the underlying mechanisms of chemotherapy resistance and develop novel potential therapeutic targets. Methods RNA sequencing of cisplatin‐resistant and ‐sensitive (chemoresistant and chemosensitive, respectively) ovarian cancer organoids was performed, followed by detection of the expression level of fibrillin‐1 (FBN1) in organoids and clinical specimens of ovarian cancer. Subsequently, glucose metabolism, angiogenesis, and chemosensitivity were analyzed in structural glycoprotein FBN1‐knockout cisplatin‐resistant ovarian cancer organoids and cell lines. To gain insights into the specific functions and mechanisms of action of FBN1 in ovarian cancer, immunoprecipitation, silver nitrate staining, mass spectrometry, immunofluorescence, Western blotting, and Fӧrster resonance energy transfer‐fluorescence lifetime imaging analyses were performed, followed by in vivo assays using vertebrate model systems of nude mice and zebrafish. Results FBN1 expression was significantly enhanced in cisplatin‐resistant ovarian cancer organoids and tissues, indicating that FBN1 might be a key factor in chemoresistance of ovarian cancer. We also discovered that FBN1 sustained the energy stress and induced angiogenesis in vitro and in vivo, which promoted the cisplatin‐resistance of ovarian cancer. Knockout of FBN1 combined with treatment of the antiangiogenic drug apatinib improved the cisplatin‐sensitivity of ovarian cancer cells. Mechanistically, FBN1 mediated the phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2) at the Tyr1054 residue, which activated its downstream focal adhesion kinase (FAK)/protein kinase B (PKB or AKT) pathway, induced the phosphorylation of signal transducer and activator of transcription 2 (STAT2) at the tyrosine residue 690 (Tyr690), promoted the nuclear translocation of STAT2, and ultimately altered the expression of genes associated with STAT2‐mediated angiogenesis and glycolysis. Conclusions The FBN1/VEGFR2/STAT2 signaling axis may induce chemoresistance of ovarian cancer cells by participating in the process of glycolysis and angiogenesis. The present study suggested a novel FBN1‐targeted therapy and/or combination of FBN1 inhibition and antiangiogenic drug for treating ovarian cancer.

As an indispensable strategy for tumor treatment, surgery may cause two major challenges: tumor recurrence and wound infection. Here, a thermoelectric therapeutic strategy is provided as either an independent cancer therapy or surgical adjuvant treatment. Bi0.5Sb1.5Te3 (BST) and Bi2Te2.8Se0.2 (BTS) nanoplates composed of Z‐scheme thermoelectric heterojunction (BST/BTS) are fabricated via a two‐step hydrothermal processes. The contact between BST and BTS constructs an interfacial electric field due to Fermi energy level rearrangement, guiding electrons in the conductive band (CB) of BTS combine with the holes in the valance band (VB) of BST, leaving stronger reduction/oxidation potentials of electrons and holes in the CB of BST and the VB of BTS. Moreover, under a mild temperature gradient, another self‐built‐in electric field is formed facilitating the migration of electrons and holes to their surfaces. Based on the PEGylated BST/BTS heterojunction, a novel thermoelectric therapy platform is developed through intravenous injection of BST/BTS and external cooling of the tumors. This thermoelectric strategy is also proved effective for combination cancer therapy with β‐elemene. Moreover, the combination of heterojunction and hydrogel is administrated on the wound after surgery, achieving efficient residual tumor treatment and antibacterial effects.

PANoptosis is a newly-discovered cell death pathway that involves crosstalk and co-ordination between pyroptosis, apoptosis, and necroptosis processes. However, the roles of PANoptosis-related genes (PRGs) in prognosis and immune landscape of colon cancer remain widely unknown. Here, we performed a bioinformatics analysis of expression data of nineteen PRGs identified from previous studies and clinical data of colon cancer patients obtained from TCGA and GEO databases. Colon cancer cases were divided into two PRG clusters, and prognosis-related differentially expressed genes (PRDEGs) were identified. The patient data were then separated into two corresponding distinct gene clusters, and the relationship between the risk score, patient prognosis, and immune landscape was analyzed. The identified PRGs and gene clusters correlated with patient survival and immune system and cancer-related biological processes and pathways. A prognosis signature based on seven genes was identified, and patients were divided into high-risk and low-risk groups based on the calculated risk score. A nomogram model for prediction of patient survival was also developed based on the risk score and other clinical features. Accordingly, the high-risk group showed worse prognosis, and the risk score was related to immune cell abundance, cancer stem cell (CSC) index, checkpoint expression, and response to immunotherapy and chemotherapeutic drugs. Results of quantitative real-time polymerase chain reaction (qRT-PCR) showed that LGR5 and VSIG4 were differentially expressed between normal and colon cancer samples. In conclusion, we demonstrated the potential of PANoptosis-based molecular clustering and prognostic signatures for prediction of patient survival and tumor microenvironment (TME) in colon cancer. Our findings may improve our understanding of the role of PANoptosis in colon cancer, and enable the development of more effective treatment strategies.