Strobel, O., Neoptolemos, J., Jager, D. & Buchler, M. W. Optimizing the outcomes of pancreatic cancer surgery. Nat. Rev. Clin. Oncol. 16, 11–26 (2019).
Google Scholar
Li, G. et al. Intersection of immune and oncometabolic pathways drives cancer hyperprogression during immunotherapy. Cancer Cell 41, 304–322 (2023).
Google Scholar
Conroy, T. et al. FOLFIRINOX or gemcitabine as adjuvant therapy for pancreatic cancer. N. Engl. J. Med. 379, 2395–2406 (2018).
Google Scholar
Siegel, R. L., Miller, K. D., Fuchs, H. E. & Jemal, A. Cancer statistics, 2022. CA Cancer J. Clin. 72, 7–33 (2022).
Google Scholar
Von Hoff, D. D. et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N. Engl. J. Med. 369, 1691–1703 (2013).
Google Scholar
Hanahan, D. Hallmarks of cancer: new dimensions. Cancer Discov. 12, 31–46 (2022).
Google Scholar
Zhao, Y. et al. Hypoxia-induced signaling in the cardiovascular system: pathogenesis and therapeutic targets. Signal Transduct. Target. Ther. 8, 431 (2023).
Google Scholar
Ivan, M. et al. Hypoxia signaling: challenges and opportunities for cancer therapy. Semin. Cancer Biol. 85, 185–195 (2022).
Google Scholar
Yoshida, G. J. Metabolic reprogramming: the emerging concept and associated therapeutic strategies. J. Exp. Clin. Cancer Res. 34, 111 (2015).
Google Scholar
Rojo de la Vega, M., Chapman, E. & Zhang, D. D. NRF2 and the hallmarks of cancer. Cancer Cell 34, 21–43 (2018).
Google Scholar
McCann, C. & Kerr, E. M. Metabolic reprogramming: a friend or foe to cancer therapy? Cancers (Basel) 13, 3351 (2021).
Google Scholar
Wang, W. et al. CD8+ T cells regulate tumour ferroptosis during cancer immunotherapy. Nature 569, 270–274 (2019).
Google Scholar
Liao, P. et al. CD8+ T cells and fatty acids orchestrate tumor ferroptosis and immunity via ACSL4. Cancer Cell 40, 365–378 (2022).
Google Scholar
Lang, X. et al. Radiotherapy and immunotherapy promote tumoral lipid oxidation and ferroptosis via synergistic repression of SLC7A11. Cancer Discov. 9, 1673–1685 (2019).
Google Scholar
Chen, X., Kang, R., Kroemer, G. & Tang, D. Broadening horizons: the role of ferroptosis in cancer. Nat. Rev. Clin. Oncol. 18, 280–296 (2021).
Google Scholar
Dixon, S. J. et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell 149, 1060–1072 (2012).
Google Scholar
Glorieux, C., Liu, S., Trachootham, D. & Huang, P. Targeting ROS in cancer: rationale and strategies. Nat. Rev. Drug Discov. 23, 583–606 (2024).
Google Scholar
Stockwell, B. R. & Jiang, X. The chemistry and biology of ferroptosis. Cell Chem. Biol. 27, 365–375 (2020).
Google Scholar
Doll, S. et al. ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition. Nat. Chem. Biol. 13, 91–98 (2017).
Google Scholar
Kagan, V. E. et al. Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis. Nat. Chem. Biol. 13, 81–90 (2017).
Google Scholar
Chen, J., Cui, L., Lu, S. & Xu, S. Amino acid metabolism in tumor biology and therapy. Cell Death Dis. 15, 42 (2024).
Google Scholar
Bidgood, C. L. et al. Targeting valine catabolism to inhibit metabolic reprogramming in prostate cancer. Cell Death Dis. 15, 513 (2024).
Google Scholar
Tajan, M. & Vousden, K. H. Dietary approaches to cancer therapy. Cancer Cell 37, 767–785 (2020).
Google Scholar
Wu, Q., Gao, Z. J., Yu, X. & Wang, P. Dietary regulation in health and disease. Signal Transduct. Target. Ther. 7, 252 (2022).
Google Scholar
El-Hachem, N. et al. Valine aminoacyl-tRNA synthetase promotes therapy resistance in melanoma. Nat. Cell Biol. 26, 1154–1164 (2024).
Google Scholar
Mayers, J. R. et al. Elevation of circulating branched-chain amino acids is an early event in human pancreatic adenocarcinoma development. Nat. Med. 20, 1193–1198 (2014).
Google Scholar
Marcadier, J. L. et al. Mutations in ALDH6A1 encoding methylmalonate semialdehyde dehydrogenase are associated with dysmyelination and transient methylmalonic aciduria. Orphanet J. Rare Dis. 8, 98 (2013).
Google Scholar
Li, X. J., Egervari, G., Wang, Y. G., Berger, S. L. & Lu, Z. M. Regulation of chromatin and gene expression by metabolic enzymes and metabolites. Nat. Rev. Mol. Cell Biol. 19, 563–578 (2018).
Google Scholar
Waby, J. S. et al. Sp1 acetylation is associated with loss of DNA binding at promoters associated with cell cycle arrest and cell death in a colon cell line. Mol. Cancer 9, 275 (2010).
Google Scholar
Zhang, Z. L. et al. Hypoxia potentiates gemcitabine-induced stemness in pancreatic cancer cells through AKT/Notch1 signaling. J. Exp. Clin. Cancer Res. 37, 291 (2018).
Google Scholar
Yang, Z. et al. HIF-1α drives resistance to ferroptosis in solid tumors by promoting lactate production and activating SLC1A1. Cell Rep. 42, 112945 (2023).
Google Scholar
Li, T., Jiang, D. & Wu, K. p62 promotes bladder cancer cell growth by activating KEAP1/NRF2-dependent antioxidative response. Cancer Sci. 111, 1156–1164 (2020).
Google Scholar
Liu, X. J. et al. Icariin inhibits hypoxia/reoxygenation-induced ferroptosis of cardiomyocytes via regulation of the Nrf2/HO-1 signaling pathway. FEBS Open Bio 11, 2966–2976 (2021).
Google Scholar
Zhang, D. et al. Metabolic regulation of gene expression by histone lactylation. Nature 574, 575–580 (2019).
Google Scholar
Chen, H. et al. NBS1 lactylation is required for efficient DNA repair and chemotherapy resistance. Nature 631, 663–669 (2024).
Google Scholar
Chen, Y. et al. Metabolic regulation of homologous recombination repair by MRE11 lactylation. Cell 187, 294–311 (2024).
Google Scholar
Chen, M. et al. NUSAP1–LDHA–glycolysis–lactate feedforward loop promotes Warburg effect and metastasis in pancreatic ductal adenocarcinoma. Cancer Lett. 567, 216285 (2023).
Google Scholar
Trefely, S., Lovell, C. D., Snyder, N. W. & Wellen, K. E. Compartmentalised acyl-CoA metabolism and roles in chromatin regulation. Mol. Metab. 38, 100941 (2020).
Google Scholar
Shang, S., Liu, J. & Hua, F. Protein acylation: mechanisms, biological functions and therapeutic targets. Signal Transduct. Target. Ther. 7, 396 (2022).
Google Scholar
Trefely, S. et al. Quantitative subcellular acyl-CoA analysis reveals distinct nuclear metabolism and isoleucine-dependent histone propionylation. Mol. Cell 82, 447–462 (2022).
Google Scholar
Kaushik, S. & Cuervo, A. M. The coming of age of chaperone-mediated autophagy. Nat. Rev. Mol. Cell Biol. 19, 365–381 (2018).
Google Scholar
Li, Z. et al. Tumor-repopulating cells evade ferroptosis via PCK2-dependent phospholipid remodeling. Nat. Chem. Biol. 20, 1341–1352 (2024).
Google Scholar
Martinez, E. et al. Human STAGA complex is a chromatin-acetylating transcription coactivator that interacts with pre-mRNA splicing and DNA damage-binding factors in vivo. Mol. Cell. Biol. 21, 6782–6795 (2001).
Google Scholar
Chatterjee, A. et al. MOF acetyl transferase regulates transcription and respiration in mitochondria. Cell 167, 722–738 (2016).
Google Scholar
Han, Z. et al. Revealing the protein propionylation activity of the histone acetyltransferase MOF (males absent on the first). J. Biol. Chem. 293, 3410–3420 (2018).
Google Scholar
Shang, M. et al. TRIM11 suppresses ferritinophagy and gemcitabine sensitivity through UBE2N/TAX1BP1 signaling in pancreatic ductal adenocarcinoma. J. Cell. Physiol. 236, 6868–6883 (2021).
Google Scholar
Mancias, J. D. et al. Ferritinophagy via NCOA4 is required for erythropoiesis and is regulated by iron dependent HERC2-mediated proteolysis. eLife 4, e10308 (2015).
Google Scholar
Lieu, E. L., Nguyen, T., Rhyne, S. & Kim, J. Amino acids in cancer. Exp. Mol. Med. 52, 15–30 (2020).
Google Scholar
Xiang, L. et al. HIF-1-dependent heme synthesis promotes gemcitabine resistance in human non-small cell lung cancers via enhanced ABCB6 expression. Cell. Mol. Life Sci. 79, 343 (2022).
Google Scholar
Klemba, A. et al. Hypoxia-mediated decrease of ovarian cancer cells reaction to treatment: significance for chemo- and immunotherapies. Int. J. Mol. Sci. 21, 9492 (2020).
Google Scholar
Springfeld, C. et al. Neoadjuvant therapy for pancreatic cancer. Nat. Rev. Clin. Oncol. 20, 318–337 (2023).
Google Scholar
Park, W., Chawla, A. & O’Reilly, E. M. Pancreatic cancer: a review. JAMA 326, 851–862 (2021).
Google Scholar
Siegel, R. L., Miller, K. D., Wagle, N. S. & Jemal, A. Cancer statistics, 2023. CA Cancer J. Clin. 73, 17–48 (2023).
Google Scholar
Zhu, Y. X. et al. LLGL1 regulates gemcitabine resistance by modulating the ERK–SP1–OSMR pathway in pancreatic ductal adenocarcinoma. Cell Mol. Gastroenterol. Hepatol. 10, 811–828 (2020).
Google Scholar
Butler, M., van der Meer, L. T. & van Leeuwen, F. N. Amino acid depletion therapies: starving cancer cells to death. Trends Endocrinol. Metab. 32, 367–381 (2021).
Google Scholar
Gao, X. et al. Dietary methionine influences therapy in mouse cancer models and alters human metabolism. Nature 572, 397–401 (2019).
Google Scholar
Ishak Gabra, M. B. et al. Dietary glutamine supplementation suppresses epigenetically-activated oncogenic pathways to inhibit melanoma tumour growth. Nat. Commun. 11, 3326 (2020).
Google Scholar
Rose, W. C., Wixom, R. L., Lockhart, H. B. & Lambert, G. F. The amino acid requirements of man. XV. The valine requirement; summary and final observations. J. Biol. Chem. 217, 987–995 (1955).
Google Scholar
Frazier, D. M. et al. Nutrition management guideline for maple syrup urine disease: an evidence- and consensus-based approach. Mol. Genet. Metab. 112, 210–217 (2014).
Google Scholar
Lei, G., Zhuang, L. & Gan, B. The roles of ferroptosis in cancer: tumor suppression, tumor microenvironment, and therapeutic interventions. Cancer Cell 42, 513–534 (2024).
Google Scholar
Xu, D. et al. The gluconeogenic enzyme PCK1 phosphorylates INSIG1/2 for lipogenesis. Nature 580, 530–535 (2020).
Google Scholar
Li, X. et al. A splicing switch from ketohexokinase-C to ketohexokinase-A drives hepatocellular carcinoma formation. Nat. Cell Biol. 18, 561–571 (2016).
Google Scholar
Qian, X. et al. PTEN suppresses glycolysis by dephosphorylating and inhibiting autophosphorylated PGK1. Mol. Cell 76, 516–527 (2019).
Google Scholar
Xu, D. et al. PAQR3 modulates cholesterol homeostasis by anchoring Scap/SREBP complex to the Golgi apparatus. Nat. Commun. 6, 8100 (2015).
Google Scholar
Dimauro, I., Pearson, T., Caporossi, D. & Jackson, M. J. A simple protocol for the subcellular fractionation of skeletal muscle cells and tissue. BMC Res. Notes 5, 513 (2012).
Google Scholar
Wang, Z. et al. Fructose-1,6-bisphosphatase 1 functions as a protein phosphatase to dephosphorylate histone H3 and suppresses PPARα-regulated gene transcription and tumour growth. Nat. Cell Biol. 24, 1655–1665 (2022).
Google Scholar
Wu, K. et al. Creatine kinase B suppresses ferroptosis by phosphorylating GPX4 through a moonlighting function. Nat. Cell Biol. 25, 714–725 (2023).
Google Scholar
Zheng, P. et al. PSAT1 impairs ferroptosis and reduces immunotherapy efficacy via GPX4 hydroxylation. Nat. Chem. Biol. 21, 1420–1432 (2025).
Google Scholar
