Oncogene-Driven Metabolic Alterations in Cancer

Overview

Journal Biomol Ther (Seoul)

Specialty Pharmacology

Date 2017 Dec 8

PMID 29212306

Citations 43

Authors

Hye-Young Min

Ho-Young Lee

Affiliations

Soon will be listed here.

Abstract

Cancer is the leading cause of human deaths worldwide. Understanding the biology underlying the evolution of cancer is important for reducing the economic and social burden of cancer. In addition to genetic aberrations, recent studies demonstrate metabolic rewiring, such as aerobic glycolysis, glutamine dependency, accumulation of intermediates of glycolysis, and upregulation of lipid and amino acid synthesis, in several types of cancer to support their high demands on nutrients for building blocks and energy production. Moreover, oncogenic mutations are known to be associated with metabolic reprogramming in cancer, and these overall changes collectively influence tumor-microenvironment interactions and cancer progression. Accordingly, several agents targeting metabolic alterations in cancer have been extensively evaluated in preclinical and clinical settings. Additionally, metabolic reprogramming is considered a novel target to control cancers harboring un-targetable oncogenic alterations such as . Focusing on lung cancer, here, we highlight recent findings regarding metabolic rewiring in cancer, its association with oncogenic alterations, and therapeutic strategies to control deregulated metabolism in cancer.

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References

Svensson R, Parker S, Eichner L, Kolar M, Wallace M, Brun S . Inhibition of acetyl-CoA carboxylase suppresses fatty acid synthesis and tumor growth of non-small-cell lung cancer in preclinical models. Nat Med. 2016; 22(10):1108-1119. PMC: 5053891. DOI: 10.1038/nm.4181. View

Dang L, Jin S, Su S . IDH mutations in glioma and acute myeloid leukemia. Trends Mol Med. 2010; 16(9):387-97. DOI: 10.1016/j.molmed.2010.07.002. View

Spees J, Olson S, Whitney M, Prockop D . Mitochondrial transfer between cells can rescue aerobic respiration. Proc Natl Acad Sci U S A. 2006; 103(5):1283-8. PMC: 1345715. DOI: 10.1073/pnas.0510511103. View

Quail D, Joyce J . Microenvironmental regulation of tumor progression and metastasis. Nat Med. 2013; 19(11):1423-37. PMC: 3954707. DOI: 10.1038/nm.3394. View

Warburg O . On the origin of cancer cells. Science. 1956; 123(3191):309-14. DOI: 10.1126/science.123.3191.309. View

Yuneva M, Fan T, Allen T, Higashi R, Ferraris D, Tsukamoto T . The metabolic profile of tumors depends on both the responsible genetic lesion and tissue type. Cell Metab. 2012; 15(2):157-70. PMC: 3282107. DOI: 10.1016/j.cmet.2011.12.015. View

Nagarajan A, Malvi P, Wajapeyee N . Oncogene-directed alterations in cancer cell metabolism. Trends Cancer. 2016; 2(7):365-377. PMC: 5096652. DOI: 10.1016/j.trecan.2016.06.002. View

Parker S, Metallo C . Metabolic consequences of oncogenic IDH mutations. Pharmacol Ther. 2015; 152:54-62. PMC: 4489982. DOI: 10.1016/j.pharmthera.2015.05.003. View

Chiaradonna F, Sacco E, Manzoni R, Giorgio M, Vanoni M, Alberghina L . Ras-dependent carbon metabolism and transformation in mouse fibroblasts. Oncogene. 2006; 25(39):5391-404. DOI: 10.1038/sj.onc.1209528. View

10.

Pakala R, Kreisel M, Bachrach U . Polyamine metabolism and interconversion in NIH 3T3 and ras-transfected NIH 3T3 cells. Cancer Res. 1988; 48(12):3336-40. View

11.

Pikor L, Ramnarine V, Lam S, Lam W . Genetic alterations defining NSCLC subtypes and their therapeutic implications. Lung Cancer. 2013; 82(2):179-89. DOI: 10.1016/j.lungcan.2013.07.025. View

12.

Hatzivassiliou G, Zhao F, Bauer D, Andreadis C, Shaw A, Dhanak D . ATP citrate lyase inhibition can suppress tumor cell growth. Cancer Cell. 2005; 8(4):311-21. DOI: 10.1016/j.ccr.2005.09.008. View

13.

Whitaker-Menezes D, Martinez-Outschoorn U, Flomenberg N, Birbe R, Witkiewicz A, Howell A . Hyperactivation of oxidative mitochondrial metabolism in epithelial cancer cells in situ: visualizing the therapeutic effects of metformin in tumor tissue. Cell Cycle. 2011; 10(23):4047-64. PMC: 3272287. DOI: 10.4161/cc.10.23.18151. View

14.

Gatenby R, Gillies R . Why do cancers have high aerobic glycolysis?. Nat Rev Cancer. 2004; 4(11):891-9. DOI: 10.1038/nrc1478. View

15.

Galluzzi L, Kepp O, Vander Heiden M, Kroemer G . Metabolic targets for cancer therapy. Nat Rev Drug Discov. 2013; 12(11):829-46. DOI: 10.1038/nrd4145. View

16.

Mailloux R . Teaching the fundamentals of electron transfer reactions in mitochondria and the production and detection of reactive oxygen species. Redox Biol. 2015; 4:381-98. PMC: 4348434. DOI: 10.1016/j.redox.2015.02.001. View

17.

Saintigny P, Burger J . Recent advances in non-small cell lung cancer biology and clinical management. Discov Med. 2012; 13(71):287-97. View

18.

Megchelenbrink W, Katzir R, Lu X, Ruppin E, Notebaart R . Synthetic dosage lethality in the human metabolic network is highly predictive of tumor growth and cancer patient survival. Proc Natl Acad Sci U S A. 2015; 112(39):12217-22. PMC: 4593091. DOI: 10.1073/pnas.1508573112. View

19.

Kurtzberg J, Asselin B, Bernstein M, Buchanan G, Pollock B, Camitta B . Polyethylene Glycol-conjugated L-asparaginase versus native L-asparaginase in combination with standard agents for children with acute lymphoblastic leukemia in second bone marrow relapse: a Children's Oncology Group Study (POG 8866). J Pediatr Hematol Oncol. 2011; 33(8):610-6. PMC: 3557823. DOI: 10.1097/MPH.0b013e31822d4d4e. View

20.

Weinberg F, Hamanaka R, Wheaton W, Weinberg S, Joseph J, Lopez M . Mitochondrial metabolism and ROS generation are essential for Kras-mediated tumorigenicity. Proc Natl Acad Sci U S A. 2010; 107(19):8788-93. PMC: 2889315. DOI: 10.1073/pnas.1003428107. View