Konstantinopoulos, P. A. & Matulonis, U. A. Clinical and translational advances in ovarian cancer therapy. Nat. Cancer 4, 1239–1257 (2023).
Henderson, J. T., Webber, E. M. & Sawaya, G. F. Screening for ovarian cancer: updated evidence report and systematic review for the us preventive services task force. JAMA 319, 595–606 (2018).
Rickard, B. P. et al. Malignant ascites in ovarian cancer: cellular, acellular, and biophysical determinants of molecular characteristics and therapy response. Cancers 13, 4318 (2021).
Luyckx, M., Squifflet, J. L., Bruger, A. M. & Baurain, J. F. in Ovarian Cancer (ed. Lele, S.) Ch. 6 (Exon Publications, 2022).
Slattery, K. et al. Uptake of lipids from ascites drives NK cell metabolic dysfunction in ovarian cancer. Sci. Immunol. 10, eadr4795 (2025).
Jagannath, A. et al. The multiple roles of salt-inducible kinases in regulating physiology. Physiol. Rev. 103, 2231–2269 (2023).
Shi, X. et al. SIK2 promotes ovarian cancer cell motility and metastasis by phosphorylating MYLK. Mol. Oncol. 16, 2558–2574 (2022).
Tarumoto, Y. et al. Salt-inducible kinase inhibition suppresses acute myeloid leukemia progression in vivo. Blood 135, 56–70 (2020).
Song, M. et al. IRE1α–XBP1 controls T cell function in ovarian cancer by regulating mitochondrial activity. Nature 562, 423–428 (2018).
Fraser, C. C. et al. Ovarian cancer ascites inhibits transcriptional activation of NK cells partly through CA125. J. Immunol. 208, 2227–2238 (2022).
Cubillos-Ruiz, J. R. et al. ER stress sensor XBP1 controls anti-tumor immunity by disrupting dendritic cell homeostasis. Cell 161, 1527–1538 (2015).
Conejo-Garcia, J. R. et al. Tumor-infiltrating dendritic cell precursors recruited by a β-defensin contribute to vasculogenesis under the influence of Vegf-A. Nat. Med. 10, 950–958 (2004).
Chae, C. S. et al. Tumor-derived lysophosphatidic acid blunts protective type i interferon responses in ovarian cancer. Cancer Discov. 12, 1904–1921 (2022).
Ding, L. et al. PARP inhibition elicits STING-dependent antitumor immunity in Brca1-deficient ovarian cancer. Cell Rep. 25, 2972–2980 (2018).
Zhou, J. et al. A novel compound ARN-3236 inhibits salt-inducible kinase 2 and sensitizes ovarian cancer cell lines and xenografts to paclitaxel. Clin. Cancer Res. 23, 1945–1954 (2017).
Lombardi, M. S., Gillieron, C., Dietrich, D. & Gabay, C. SIK inhibition in human myeloid cells modulates TLR and IL-1R signaling and induces an anti-inflammatory phenotype. J. Leukoc. Biol. 99, 711–721 (2016).
Sundberg, T. B. et al. Small-molecule screening identifies inhibition of salt-inducible kinases as a therapeutic strategy to enhance immunoregulatory functions of dendritic cells. Proc. Natl Acad. Sci. USA 111, 12468–12473 (2014).
Park, S. A. et al. IA-0130, a novel 3-(1,3-diarylallylidene)oxindole derivative, alleviates ovarian cancer via inhibiting IL-6/gp130/STAT3 signalling. Br. J. Pharmacol. 182, 5670–5689 (2025).
Amer, H. et al. Interleukin-6 is a crucial factor in shaping the inflammatory tumor microenvironment in ovarian cancer and determining its hot or cold nature with diagnostic and prognostic utilities. Cancers 17, 1691 (2025).
Devenport, J. M. et al. APOBEC3A drives ovarian cancer metastasis by altering epithelial–mesenchymal transition. JCI Insight 10, e186409 (2025).
Yoon, S. H. et al. A parathyroid hormone/salt-inducible kinase signaling axis controls renal vitamin D activation and organismal calcium homeostasis. J. Clin. Invest. 133, e163627 (2023).
Nefla, M., Darling, N. J., van Gijsel Bonnello, M., Cohen, P. & Arthur, J. S. C. Salt inducible kinases 2 and 3 are required for thymic T cell development. Sci. Rep. 11, 21550 (2021).
Salerno, F. et al. Translational repression of pre-formed cytokine-encoding mRNA prevents chronic activation of memory T cells. Nat. Immunol. 19, 828–837 (2018).
Moore, M. J. et al. ZFP36 RNA-binding proteins restrain T cell activation and anti-viral immunity. eLife 7, e33057 (2018).
Muri, J., Thut, H. & Kopf, M. The thioredoxin-1 inhibitor Txnip restrains effector T-cell and germinal center B-cell expansion. Eur. J. Immunol. 51, 115–124 (2021).
Malone, C. F. et al. mTOR and HDAC inhibitors converge on the TXNIP/Thioredoxin pathway to cause catastrophic oxidative stress and regression of RAS-driven tumors. Cancer Discov. 7, 1450–1463 (2017).
Alhawiti, N. M., Al Mahri, S., Aziz, M. A., Malik, S. S. & Mohammad, S. TXNIP in metabolic regulation: physiological role and therapeutic outlook. Curr. Drug Targets 18, 1095–1103 (2017).
Lerner, A. G. et al. IRE1α induces thioredoxin-interacting protein to activate the NLRP3 inflammasome and promote programmed cell death under irremediable ER stress. Cell Metab. 16, 250–264 (2012).
Cao, J. et al. Effects of altered glycolysis levels on CD8+ T cell activation and function. Cell Death Dis. 14, 407 (2023).
Sharma, P. et al. Chediak–Higashi syndrome: a review of the past, present, and future. Drug Discov. Today Dis. Models 31, 31–36 (2020).
Barbosa, M. D. et al. Identification of the homologous beige and Chediak–Higashi syndrome genes. Nature 382, 262–265 (1996).
Mollaoglu, G. et al. Ovarian cancer-derived IL-4 promotes immunotherapy resistance. Cell 187, 7492–7510 (2024).
Li, J. et al. Serotonin-licensed macrophages potentiate chemoresistance via inositol metabolic crosstalk in ovarian cancer. Cell Metab. 38, 331–349 (2025).
Sundberg, T. B. et al. Development of chemical probes for investigation of salt-inducible kinase function in vivo. ACS Chem. Biol. 11, 2105–2111 (2016).
Lu, Z. et al. SIK2 inhibition enhances PARP inhibitor activity synergistically in ovarian and triple-negative breast cancers. J. Clin. Invest. 132, e146471 (2022).
Fan, D. et al. A novel salt inducible kinase 2 inhibitor, ARN-3261, sensitizes ovarian cancer cell lines and xenografts to carboplatin. Cancers 13, 446 (2021).
Hua, Y. et al. Salt-inducible kinase 2-triggered release of its inhibitor from hydrogel to suppress ovarian cancer metastasis. Adv. Sci. 9, e2202260 (2022).
Tang, C. C. et al. Dual targeting of salt inducible kinases and CSF1R uncouples bone formation and bone resorption. eLife 10, e67772 (2021).
Rachmin, I. et al. A novel approach to target skin photodamage: topical application of salt inducible kinase inhibitors. Int. J. Cosmet. Sci. 48, 1–15 (2025).
Medina, C. B. et al. Pannexin 1 channels facilitate communication between T cells to restrict the severity of airway inflammation. Immunity 54, 1715–1727 (2021).
Helms, R. S. et al. SIKs regulate HDAC7 stabilization and cytokine recall in late-stage T cell effector differentiation. J. Immunol. 211, 1767–1782 (2023).
Poffenberger, M. C. et al. LKB1 deficiency in T cells promotes the development of gastrointestinal polyposis. Science 361, 406–411 (2018).
Xu, N. et al. Targeting MondoA–TXNIP restores antitumour immunity in lactic-acid-induced immunosuppressive microenvironment. Nat. Metab. 7, 1889–1904 (2025).
Sullivan, W. J. et al. Extracellular matrix remodeling regulates glucose metabolism through TXNIP destabilization. Cell 175, 117–132 (2018).
Oh, D. Y. & Fong, L. Cytotoxic CD4+ T cells in cancer: expanding the immune effector toolbox. Immunity 54, 2701–2711 (2021).
Ovarian Tumor Tissue Analysis Consortium et al. Dose-response association of CD8+ tumor-infiltrating lymphocytes and survival time in high-grade serous ovarian cancer. JAMA Oncol. 3, e173290 (2017).
Hor, J. L. et al. Inhibitory PD-1 axis maintains high-avidity stem-like CD8+ T cells. Nature 649, 194–204 (2026).
Jang, M. et al. Characterization of T cell repertoire of blood, tumor, and ascites in ovarian cancer patients using next generation sequencing. Oncoimmunology 4, e1030561 (2015).
Zheng, X. et al. Single-cell analyses implicate ascites in remodeling the ecosystems of primary and metastatic tumors in ovarian cancer. Nat. Cancer 4, 1138–1156 (2023).
Lee, W. et al. Neutrophil extracellular traps promote pre-metastatic niche formation in the omentum by expanding innate-like B cells that express IL-10. Cancer Cell 43, 69–85 (2025).
Patel, K. et al. The LKB1-salt-inducible kinase pathway functions as a key gluconeogenic suppressor in the liver. Nat. Commun. 5, 4535 (2014).
Nishimori, S. et al. Salt-inducible kinases dictate parathyroid hormone 1 receptor action in bone development and remodeling. J. Clin. Invest. 129, 5187–5203 (2019).
Patel, R., Czapar, A. E., Fiering, S., Oleinick, N. L. & Steinmetz, N. F. Radiation therapy combined with cowpea mosaic virus nanoparticle in situ vaccination initiates immune-mediated tumor regression. ACS Omega 3, 3702–3707 (2018).
Scrucca, L., Fop, M., Murphy, T. B. & Raftery, A. E. mclust 5: Clustering, classification and density estimation using gaussian finite mixture models. R J. 8, 289–317 (2016).
Hafemeister, C. & Satija, R. Normalization and variance stabilization of single-cell RNA-seq data using regularized negative binomial regression. Genome Biol. 20, 296 (2019).
Hao, Y. et al. Integrated analysis of multimodal single-cell data. Cell 184, 3573–3587 (2021).
Aran, D. et al. Reference-based analysis of lung single-cell sequencing reveals a transitional profibrotic macrophage. Nat. Immunol. 20, 163–172 (2019).
Benayoun, B. A. et al. Remodeling of epigenome and transcriptome landscapes with aging in mice reveals widespread induction of inflammatory responses. Genome Res. 29, 697–709 (2019).
Robinson, M. D., McCarthy, D. J. & Smyth, G. K. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26, 139–140 (2010).
Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014).
Hochberg, Y. & Benjamini, Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J. R. Stat. Soc. B 57, 289–300 (1995).
Wu, T. et al. clusterProfiler 4.0: A universal enrichment tool for interpreting omics data. Innovation 2, 100141 (2021).
Black, S. et al. CODEX multiplexed tissue imaging with DNA-conjugated antibodies. Nat. Protoc. 16, 3802–3835 (2021).
Hwang, S. M. et al. Transgelin 2 guards T cell lipid metabolism and antitumour function. Nature 635, 1010–1018 (2024).

















Leave a Reply