Systemic Oncology: Metabolic, Immune, and Endocrine Mechanisms in Tumor Progression
DOI:
https://doi.org/10.64784/214Palabras clave:
Cancer metabolism, tumor progression, immunometabolism, endocrine dysfunction, chronic inflammation, tumor microenvironment, immune evasion, cancer cachexia, metabolic reprogramming, oncology, systemic disease, therapeutic resistanceResumen
Cancer is currently recognized as a systemic and multifactorial disease involving complex interactions between metabolism, immunity, endocrinology, inflammation, and the tumor microenvironment. The objective of this review was to analyze the metabolic and immune interactions involved in tumor progression from an integrative systemic perspective. A narrative review methodology was employed using scientific literature indexed in PubMed, Scopus, Web of Science, and ScienceDirect between 2020 and 2025. The analyzed evidence demonstrated that tumor progression depends not only on genetic alterations but also on metabolic reprogramming, chronic inflammatory signaling, endocrine dysfunction, immune suppression, and adaptive modifications within the tumor microenvironment. Malignant cells exhibit metabolic flexibility characterized by increased glycolysis, glutamine dependency, altered lipid metabolism, and mitochondrial adaptations that promote survival under hypoxic and nutrient-deprived conditions. Simultaneously, metabolic competition and accumulation of immunosuppressive metabolites impair cytotoxic immune responses and favor immune evasion. Obesity, insulin resistance, hyperinsulinemia, adipokine imbalance, and chronic low-grade inflammation were identified as important systemic contributors to carcinogenesis and tumor dissemination. The review additionally highlighted the relevance of cancer-associated cachexia, chronic inflammation, and therapeutic resistance as systemic manifestations of malignant disease. Current evidence supports the development of integrated therapeutic strategies combining metabolic modulation, immunotherapy, endocrine intervention, and anti-inflammatory approaches. Overall, this review reinforces the concept that cancer progression results from continuous communication between malignant cells and host physiology, emphasizing the importance of multidisciplinary and systemic perspectives in contemporary oncology.
Referencias
• Swanton, C., Bernard, E., Abbosh, C., Andre, F., Auwerx, J., Balmain, A., Bartek, J., Bernards, R., Birkbak, N. J., Bissell, M. J., et al. (2024). Embracing cancer complexity: Hallmarks of systemic disease. Cell. https://doi.org/10.1016/j.cell.2024.02.009
• Hanahan, D. (2022). Hallmarks of cancer: New dimensions. Cancer Discovery, 12(1), 31–46. https://doi.org/10.1158/2159-8290.CD-21-1059
• Faubert, B., Solmonson, A., & DeBerardinis, R. J. (2020). Metabolic reprogramming and cancer progression. Science, 368(6487), eaaw5473. https://doi.org/10.1126/science.aaw5473
• Pavlova, N. N., & Thompson, C. B. (2022). The hallmarks of cancer metabolism: Still emerging. Cell Metabolism, 34(3), 355–377. https://doi.org/10.1016/j.cmet.2022.01.007
• Pavlova, N. N., & Thompson, C. B. (2016). The emerging hallmarks of cancer metabolism. Cell Metabolism, 23(1), 27–47. https://doi.org/10.1016/j.cmet.2015.12.006
• Vander Heiden, M. G., & DeBerardinis, R. J. (2017). Understanding the intersections between metabolism and cancer biology. Cell, 168(4), 657–669. https://doi.org/10.1016/j.cell.2016.12.039
• Leone, R. D., & Powell, J. D. (2020). Metabolism of immune cells in cancer. Nature Reviews Cancer, 20(9), 516–531. https://doi.org/10.1038/s41568-020-0273-y
• De Martino, M., Rathmell, J. C., Galluzzi, L., & Vanpouille-Box, C. (2024). Cancer cell metabolism and antitumour immunity. Nature Reviews Immunology, 24(9). https://doi.org/10.1038/s41577-024-01026-4
• Chuang, Y. M., Tzeng, S. F., Ho, P. C., & Tsai, C. H. (2024). Immunosurveillance encounters cancer metabolism. Nature Cancer. https://doi.org/10.1038/s44319-023-00038-w
• Zhang, H., Li, S., Wang, D., & Zhang, Y. (2024). Metabolic reprogramming and immune evasion: The interplay in the tumor microenvironment. Biomarker Research, 12, Article 93. https://doi.org/10.1186/s40364-024-00646-1
• Xia, L., Oyang, L., Lin, J., Tan, S., Han, Y., Wu, N., Yi, P., Tang, L., Pan, Q., Rao, S., Liang, J., Tang, Y., Su, M., Luo, X., Yang, Y., Shi, Y., Wang, H., Zhou, Y., Liao, Q., & Wang, H. (2021). The cancer metabolic reprogramming and immune response. Molecular Cancer, 20, Article 28. https://doi.org/10.1186/s12943-021-01316-8
• Finley, L. W. S. (2023). What is cancer metabolism? Cell, 186(8), 1670–1688. https://doi.org/10.1016/j.cell.2023.01.038
• Vella, V., Nicolosi, M. L., Cantafio, P., Massimino, M., Lappano, R., Vigneri, P., Belfiore, A., & Malaguarnera, R. (2023). Insulin/IGF axis and the receptor for advanced glycation end products in cancer. Endocrine Reviews, 44(4), 693–723. https://doi.org/10.1210/endrev/bnad003
• Kim, D. S., Scherer, P. E., & Chan, H. Y. (2021). Obesity, diabetes, and increased cancer progression. Diabetes & Metabolism Journal, 45(6), 799–812. https://doi.org/10.4093/dmj.2021.0077
• Zhong, W., Deng, Q., Deng, X., Zhong, Z., Hou, J., & Chen, Y. (2023). Obesity and endocrine-related cancer: The important role of sex hormones. Frontiers in Endocrinology, 14, 1099495. https://doi.org/10.3389/fendo.2023.1099495
• Ruze, R., Liu, T., Zou, X., Song, J., Chen, Y., Xu, R., Yin, X., & Xu, Q. (2023). Mechanisms of obesity- and diabetes mellitus-related pancreatic carcinogenesis: A comprehensive and critical review. Signal Transduction and Targeted Therapy, 8, Article 139. https://doi.org/10.1038/s41392-023-01367-w
• Wu, Q., Chen, X., Liu, J., & Wang, X. (2023). Immunoregulation in cancer-associated cachexia. Frontiers in Immunology, 14, 1149925. https://doi.org/10.3389/fimmu.2023.1149925
• Da Silva, S. P., Santos, J. M. O., Costa E Silva, M. P., Gil da Costa, R. M., & Medeiros, R. (2020). Cancer cachexia and its pathophysiology: Links with sarcopenia, anorexia and asthenia. Journal of Cachexia, Sarcopenia and Muscle, 11(3), 619–635. https://doi.org/10.1002/jcsm.12528
• Altea-Manzano, P., Doglioni, G., Galluzzi, L., & Kroemer, G. (2025). Metabolic interplays between the tumor and the host shape cancer progression and therapy response. Nature Reviews Cancer. https://doi.org/10.1038/s41568-025-00796-y
• Hu, T., Liu, Y., & Chen, L. (2024). Metabolic regulation of the immune system in health and disease. Signal Transduction and Targeted Therapy, 9, Article 202. https://doi.org/10.1038/s41392-024-01954-6
