Quintas-Cardama, A., Kantarjian, H. & Cortes, J. Flying under the radar: the new wave of BCR–ABL inhibitors. Nat. Rev. Drug Discov. 6, 834–848 (2007).
Google Scholar
Wong, S. & Witte, O. N. The BCR–ABL story: bench to bedside and back. Annu. Rev. Immunol. 22, 247–306 (2004).
Google Scholar
Nelson, K. N., Peiris, M. N., Meyer, A. N., Siari, A. & Donoghue, D. J. Receptor tyrosine kinases: translocation partners in hematopoietic disorders. Trends Mol. Med. 23, 59–79 (2017).
Google Scholar
Schindler, T. et al. Structural mechanism for STI-571 inhibition of abelson tyrosine kinase. Science 289, 1938–1942 (2000).
Google Scholar
Mauro, M. J. & Druker, B. J. STI571: a gene product-targeted therapy for leukemia. Curr. Oncol. Rep. 3, 223–227 (2001).
Google Scholar
Kantarjian, H. et al. Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N. Engl. J. Med. 346, 645–652 (2002).
Google Scholar
Gorre, M. E. et al. Clinical resistance to STI-571 cancer therapy caused by BCR–ABL gene mutation or amplification. Science 293, 876–880 (2001).
Google Scholar
Shah, N. P. et al. Multiple BCR–ABL kinase domain mutations confer polyclonal resistance to the tyrosine kinase inhibitor imatinib (STI571) in chronic phase and blast crisis chronic myeloid leukemia. Cancer Cell 2, 117–125 (2002).
Google Scholar
Mao, Y., Xia, Z., Xia, W. & Jiang, P. Metabolic reprogramming, sensing, and cancer therapy. Cell Rep. 43, 115064 (2024).
Google Scholar
DeBerardinis, R. J. & Thompson, C. B. Cellular metabolism and disease: what do metabolic outliers teach us? Cell 148, 1132–1144 (2012).
Google Scholar
De Martino, M., Rathmell, J. C., Galluzzi, L. & Vanpouille-Box, C. Cancer cell metabolism and antitumour immunity. Nat. Rev. Immunol. 24, 654–669 (2024).
Google Scholar
Stine, Z. E., Schug, Z. T., Salvino, J. M. & Dang, C. V. Targeting cancer metabolism in the era of precision oncology. Nat. Rev. Drug Discov. 21, 141–162 (2022).
Google Scholar
Koppenol, W. H., Bounds, P. L. & Dang, C. V. Otto Warburg’s contributions to current concepts of cancer metabolism. Nat. Rev. Cancer 11, 325–337 (2011).
Google Scholar
Hay, N. Reprogramming glucose metabolism in cancer: can it be exploited for cancer therapy? Nat. Rev. Cancer 16, 635–649 (2016).
Google Scholar
Bensaad, K. et al. TIGAR, a p53-inducible regulator of glycolysis and apoptosis. Cell 126, 107–120 (2006).
Google Scholar
Jiang, P. et al. p53 regulates biosynthesis through direct inactivation of glucose-6-phosphate dehydrogenase. Nat. Cell Biol. 13, 310–316 (2011).
Google Scholar
Li, L. et al. p53 regulation of ammonia metabolism through urea cycle controls polyamine biosynthesis. Nature 567, 253–256 (2019).
Google Scholar
Wise, D. R. et al. Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction. Proc. Natl Acad. Sci. USA 105, 18782–18787 (2008).
Google Scholar
Gao, P. et al. c-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism. Nature 458, 762–765 (2009).
Google Scholar
Mao, Y., Xia, W. & Jiang, P. Metabolites as signalling molecules in the tumour immune microenvironment. Nat. Rev. Immunol. 26, 422–438 https://doi.org/10.1038/s41577-025-01258-y (2026).
Hajaj, E., Sciacovelli, M., Frezza, C. & Erez, A. The context-specific roles of urea cycle enzymes in tumorigenesis. Mol. Cell 81, 3749–3759 (2021).
Google Scholar
Hooftman, A. et al. Macrophage fumarate hydratase restrains mtRNA-mediated interferon production. Nature 615, 490–498 (2023).
Google Scholar
Mao, Y., Shi, D., Li, G. & Jiang, P. Citrulline depletion by ASS1 is required for proinflammatory macrophage activation and immune responses. Mol. Cell 82, 527–541.e7 (2022).
Google Scholar
Husson, A., Brasse-Lagnel, C., Fairand, A., Renouf, S. & Lavoinne, A. Argininosuccinate synthetase from the urea cycle to the citrulline–NO cycle. Eur. J. Biochem. 270, 1887–1899 (2003).
Google Scholar
van de Poll, M. C. et al. Interorgan amino acid exchange in humans: consequences for arginine and citrulline metabolism. Am. J. Clin. Nutr. 85, 167–172 (2007).
Google Scholar
Zhou, J., Sun, X. & Jiang, P. The emerging roles of the urea cycle in tumor microenvironment and therapies. Trends Cancer 11, 1203–1219 (2025).
Google Scholar
Lee, J. S. et al. Urea cycle dysregulation generates clinically relevant genomic and biochemical signatures. Cell 174, 1559–1570.e22 (2018).
Google Scholar
Kim, J. et al. CPS1 maintains pyrimidine pools and DNA synthesis in KRAS/LKB1-mutant lung cancer cells. Nature 546, 168–172 (2017).
Google Scholar
Rabinovich, S. et al. Diversion of aspartate in ASS1-deficient tumours fosters de novo pyrimidine synthesis. Nature 527, 379–383 (2015).
Google Scholar
Lim, L. Q. J. et al. ASS1 metabolically contributes to the nuclear and cytosolic p53-mediated DNA damage response. Nat. Metab. 6, 1294–1309 (2024).
Google Scholar
Keshet, R. et al. Targeting purine synthesis in ASS1-expressing tumors enhances the response to immune checkpoint inhibitors. Nat. Cancer 1, 894–908 (2020).
Google Scholar
Yang, H. et al. A commensal protozoan attenuates Clostridioides difficile pathogenesis in mice via arginine-ornithine metabolism and host intestinal immune response. Nat. Commun. 15, 2842 (2024).
Google Scholar
Gorgoglione, R. et al. Glutamine-derived aspartate biosynthesis in cancer cells: role of mitochondrial transporters and new therapeutic perspectives. Cancers (Basel) 14, 245 https://doi.org/10.3390/cancers14010245 (2022).
Tozzi, M. G., Pesi, R. & Allegrini, S. On the physiological role of cytosolic 5′-nucleotidase II (cN-II): pathological and therapeutical implications. Curr. Med. Chem. 20, 4285–4291 (2013).
Google Scholar
Paglia, D. E. & Valentine, W. N. Characteristics of a pyrimidine-specific 5′-nucleotidase in human erythrocytes. J. Biol. Chem. 250, 7973–7979 (1975).
Google Scholar
Dieck, C. L. et al. Structure and mechanisms of NT5C2 mutations driving thiopurine resistance in relapsed lymphoblastic leukemia. Cancer Cell 34, 136–147.e6 (2018).
Google Scholar
Zheng, L. et al. Reversed argininosuccinate lyase activity in fumarate hydratase-deficient cancer cells. Cancer Metab. 1, 12 (2013).
Google Scholar
Dunlap, K. N. et al. SLC7A5 is required for cancer cell growth under arginine-limited conditions. Cell Rep. 44, 115130 (2025).
Google Scholar
Nwosu, Z. C. et al. Uridine-derived ribose fuels glucose-restricted pancreatic cancer. Nature 618, 151–158 (2023).
Google Scholar
Skinner, O. S. et al. Salvage of ribose from uridine or RNA supports glycolysis in nutrient-limited conditions. Nature Metab. 5, 765–776 (2023).
Google Scholar
King, M. P. & Attardi, G. Human cells lacking mtDNA: repopulation with exogenous mitochondria by complementation. Science 246, 500–503 (1989).
Google Scholar
Sharma, A. K., Khandelwal, R. & Wolfrum, C. Futile cycles: emerging utility from apparent futility. Cell Metab. 36, 1184–1203 (2024).
Google Scholar
Heng, T. S. P. et al. The Immunological Genome Project: networks of gene expression in immune cells. Nat. Immunol. 9, 1091–1094 (2008).
Google Scholar
Cerami, E. et al. The cBio Cancer Genomics Portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2, 401–404 (2012).
Google Scholar
Jin, H. et al. Systematic transcriptional analysis of human cell lines for gene expression landscape and tumor representation. Nat. Commun. 14, 5417 https://doi.org/10.1038/s41467-023-41132-w (2023).
