Exploiting Cancer Cells Metabolic Adaptability to Enhance Therapy Response in Cancer
- 211 Downloads
Despite all the progresses developed in prevention and new treatment approaches, cancer is the second leading cause of death worldwide, being chemoresistance a pivotal barrier in cancer management. Cancer cells present several mechanisms of drug resistance/tolerance and recently, growing evidence have been supporting a role of metabolism reprograming per se as a driver of chemoresistance. In fact, cancer cells display several adaptive mechanisms that allow the emergency of chemoresistance, revealing cancer as a disease that adapts and evolve along with the treatment. Therefore, clinical protocols that take into account the adaptive potential of cancer cells should be more effective than the current traditional standard protocols on the fighting against cancer.
In here, some of the recent findings on the role of metabolism reprograming in cancer chemoresistance emergence will be discussed, as the potential evolutionary strategies that could unable these adaptations, hence allowing to prevent the emergency of treatment resistance, changing cancer outcome.
KeywordsAdaptation Cancer Chemoresistance Evolution Metabolism
The authors acknowledge iNOVA4Health – UID/Multi/04462/2013, a program financially supported by Fundação para a Ciência e Tecnologia/Ministério da Educação e Ciência, through national funds and co-funded by FEDER under the PT2020 Partnership Agreement.
- Ahmed N, Escalona R, Leung D, Chan E, Kannourakis G (2018) Tumour microenvironment and metabolic plasticity in cancer and cancer stem cells: perspectives on metabolic and immune regulatory signatures in chemoresistant ovarian cancer stem cells. Semin Cancer Biol 53:265–281. https://doi.org/10.1016/J.SEMCANCER.2018.10.002CrossRefPubMedGoogle Scholar
- Alam MM, Lal S, FitzGerald KE, Zhang L (2016) A holistic view of cancer bioenergetics: mitochondrial function and respiration play fundamental roles in the development and progression of diverse tumors. Clin Transl Med 5(3). https://doi.org/10.1186/s40169-016-0082-9
- Datta S, Choudhury D, Das A, Das Mukherjee D, Das N, Roy SS, Chakrabarti G (2017) Paclitaxel resistance development is associated with biphasic changes in reactive oxygen species, mitochondrial membrane potential and autophagy with elevated energy production capacity in lung cancer cells: a chronological study. Tumor Biol 39:1–14. https://doi.org/10.1177/1010428317694314CrossRefGoogle Scholar
- Deblois G, Tonekaboni SAM, Kao YI, Tai F, Liu X, Ettayebi I et al (2018) Metabolic adaptations underlie epigenetic vulnerabilities in chemoresistant breast cancer. bioRxiv:1–51. https://doi.org/10.1101/286054
- Enriquez-navas PM, and Gatenby RA (2017) Applying tools from evolutionary biology to cancer research. Ecol Evol Cancer. Chapter 14:193–200. https://doi.org/10.1016/B978-0-12-804310-3/00014-4
- Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C et al. (2013a) GLOBOCAN 2012a v1.0, cancer incidence and mortality worldwide: IARC cancerbase No. 11. Retrieved August 24, 2018, from http://globocan.iarc.fr
- Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C et al. (2013b) GLOBOCAN 2012b v1.0, cancer incidence and mortality worldwide: IARC cancerbase no. 11. Retrieved August 30, 2018, from http://globocan.iarc.fr
- Gallaher JA, Enriquez-Navas PM, Luddy KA, Gatenby RA, Anderson ARA (2017) Spatial heterogeneity and evolutionary dynamics modulate time to recurrence in continuous and adaptive cancer therapies. bioRxiv:1–21. https://doi.org/10.1101/128959
- Gallipoli P, Giotopoulos G, Tzelepis K, Costa ASH, Vohra S, Medina-Perez P et al (2018) Glutaminolysis is a metabolic dependency in FLT3ITDacute myeloid leukemia unmasked by FLT3 tyrosine kinase inhibition. Blood 131:1639–1653. https://doi.org/10.1182/blood-2017-12-820035CrossRefPubMedPubMedCentralGoogle Scholar
- Gastel N, van Schajnovitz A, Vidoudez C, Oki T, Sharda A, Trauger SA, Scadden DT (2017) Untargeted metabolomics identifies glutamine metabolism as a driver of chemoresistance in acute myeloid Leukemia. Blood 130:2523Google Scholar
- Gottesman MM (2002) Mechanisms of cancer drug resistance. Annu Rev Med 53:615–627. https://doi.org/10.1146/annurev.med.53.082901.103929CrossRefPubMedGoogle Scholar
- Khamari R, Trinh A, Gabert PE, Corazao-Rozas P, Riveros-Cruz S, Balayssac S et al (2018) Glucose metabolism and NRF2 coordinate the antioxidant response in melanoma resistant to MAPK inhibitors. Cell Death Dis 9:325–338. https://doi.org/10.1038/s41419-018-0340-4CrossRefPubMedPubMedCentralGoogle Scholar
- Lopes-Coelho F, Nunes C, Gouveia-Fernandes S, Rosas R, Silva F, Gameiro P et al (2017) Monocarboxylate transporter 1 (MCT1), a tool to stratify acute myeloid leukemia (AML) patients and a vehicle to kill cancer cells. Oncotarget 8:82803–82823. https://doi.org/10.18632/oncotarget.20294CrossRefPubMedPubMedCentralGoogle Scholar
- Rodríguez-Enríquez S, Vital-González PA, Flores-Rodríguez FL, Marín-Hernández A, Ruiz-Azuara L, Moreno-Sánchez R (2006) Control of cellular proliferation by modulation of oxidative phosphorylation in human and rodent fast-growing tumor cells. Toxicol Appl Pharmacol 215:208–217. https://doi.org/10.1016/j.taap.2006.02.005CrossRefPubMedGoogle Scholar
- Yu L, Lu M, Jia D, Ma J, Ben-Jacob E, Levine H et al (2017) Modeling the genetic regulation of cancer metabolism: interplay between glycolysis and oxidative phosphorylation. Cancer Res 77:1564–1574. https://doi.org/10.1158/0008-5472.CAN-16-2074.ModelingCrossRefPubMedPubMedCentralGoogle Scholar
- Zhang J, Cunningham JJ, Brown JS, Gatenby RA (2017b) Integrating evolutionary dynamics into treatment of metastatic castrate-resistant prostate cancer. Nat Commun 8:1–9. https://doi.org/10.1038/s41467-017-01968-5
- Zhao JG, Ren KM, Tang J (2014) Overcoming 5-Fu resistance in human non-small cell lung cancer cells by the combination of 5-Fu and cisplatin through the inhibition of glucose metabolism. Tumor Biol 35:12305–12315. https://doi.org/10.11862/CJIC.2015.154