Targeting Cell Metabolism as Cancer Therapy

被引:40
作者
Ngoi, Natalie Y. L. [1 ]
Eu, Jie Qing [2 ,3 ,4 ]
Hirpara, Jayshree [2 ,3 ,4 ]
Wang, Lingzhi [4 ]
Lim, Joline S. J. [1 ]
Lee, Soo-Chin [1 ,4 ]
Lim, Yaw-Chyn [2 ,3 ]
Pervaiz, Shazib [2 ,3 ,5 ,6 ]
Goh, Boon Cher [1 ,4 ]
Wong, Andrea L. A. [1 ,4 ]
机构
[1] Natl Univ Canc Inst, Dept Haematol Oncol, 1E Lower Kent Ridge Rd, Singapore, Singapore
[2] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Physiol, Singapore, Singapore
[3] Natl Univ Singapore, Yong Loo Lin Sch Med, Med Sci Cluster Canc Program, Singapore, Singapore
[4] Natl Univ Singapore, Canc Sci Inst, Singapore, Singapore
[5] Natl Univ Singapore, NUS Grad Sch Integrat Sci & Engn, Singapore, Singapore
[6] Natl Univ Hlth Syst, Natl Univ Canc Inst, Singapore, Singapore
基金
英国医学研究理事会;
关键词
cell metabolism; cancer therapy; metabolic vulnerability; FATTY-ACID SYNTHASE; ATP-CITRATE LYASE; ACUTE MYELOID-LEUKEMIA; OXIDATIVE-PHOSPHORYLATION INHIBITOR; PYRUVATE-KINASE; SMALL-MOLECULE; PHASE-I; PANCREATIC-CANCER; UP-REGULATION; LUNG-CANCER;
D O I
10.1089/ars.2019.7947
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
-oxidation needs during tumor proliferation and metastasis. The common induction of metabolic pathways during cancer progression, regardless of cancer histio- or genotype, makes cancer metabolism an attractive target for therapeutic exploitation. Recent Advances: Emerging data suggest that these altered pathways may even result in resistance to anticancer therapies. Identifying specific metabolic dependencies that are unique to cancer cells has proved challenging in this field, limiting the therapeutic window for many candidate drug approaches. Critical Issues: Cancer cells display significant metabolic flexibility in nutrient-limited environments, hampering the longevity of suppressing cancer metabolism through any singular approach. Combinatorial "synthetic lethal" approaches may have a better chance for success and promising strategies are reviewed here. The dynamism of the immune system adds a level of complexity, as various immune populations in the tumor microenvironment often share metabolic pathways with cancer, with successive alterations during immune activation and quiescence. Decoding the reprogramming of metabolic pathways within cancer cells and stem cells, as well as examining metabolic symbiosis between components of the tumor microenvironment, would be essential to further meaningful drug development within the tumor's metabolic ecosystem. Future Directions: In this article, we examine evidence for the therapeutic potential of targeting metabolic alterations in cancer, and we discuss the drawbacks and successes that have stimulated this field.
引用
收藏
页码:285 / 308
页数:24
相关论文
共 178 条
[1]   Mechanisms of Resistance to EGFR Tyrosine Kinase Inhibitors and Therapeutic Approaches: An Update [J].
Ahsan, Aarif .
LUNG CANCER AND PERSONALIZED MEDICINE: CURRENT KNOWLEDGE AND THERAPIES, 2016, 893 :137-153
[2]   Diet and tumor LKB1 expression interact to determine sensitivity to anti-neoplastic effects of metformin in vivo [J].
Algire, C. ;
Amrein, L. ;
Bazile, M. ;
David, S. ;
Zakikhani, M. ;
Pollak, M. .
ONCOGENE, 2011, 30 (10) :1174-1182
[3]   Safety and tolerability of the first-in-class agent CPI-613 in combination with modified FOLFIRINOX in patients with metastatic pancreatic cancer: a single-centre, open-label, dose-escalation, phase 1 trial [J].
Alistar, Angela ;
Morris, Bonny B. ;
Desnoyer, Rodwige ;
Klepin, Heidi D. ;
Hosseinzadeh, Keyanoosh ;
Clark, Clancy ;
Cameron, Amy ;
Leyendecker, John ;
D'Agostino, Ralph, Jr. ;
Topaloglu, Umit ;
Boteju, Lakmal W. ;
Boteju, Asela R. ;
Shorr, Rob ;
Zachar, Zuzana ;
Bingham, Paul M. ;
Ahmed, Tamjeed ;
Crane, Sandrine ;
Shah, Riddhishkumar ;
Migliano, John J. ;
Pardee, Timothy S. ;
Miller, Lance ;
Hawkins, Gregory ;
Jin, Guangxu ;
Zhang, Wei ;
Pasche, Boris .
LANCET ONCOLOGY, 2017, 18 (06) :770-778
[4]   From Krebs to clinic: glutamine metabolism to cancer therapy [J].
Altman, Brian J. ;
Stine, Zachary E. ;
Dang, Chi V. .
NATURE REVIEWS CANCER, 2016, 16 (10) :619-634
[5]  
[Anonymous], 2019, J CLIN ONCOL S
[6]   A guide to 13C metabolic flux analysis for the cancer biologist [J].
Antoniewicz, Maciek R. .
EXPERIMENTAL AND MOLECULAR MEDICINE, 2018, 50 :1-13
[7]   The Genotype-Tissue Expression (GTEx) pilot analysis: Multitissue gene regulation in humans [J].
Ardlie, Kristin G. ;
DeLuca, David S. ;
Segre, Ayellet V. ;
Sullivan, Timothy J. ;
Young, Taylor R. ;
Gelfand, Ellen T. ;
Trowbridge, Casandra A. ;
Maller, Julian B. ;
Tukiainen, Taru ;
Lek, Monkol ;
Ward, Lucas D. ;
Kheradpour, Pouya ;
Iriarte, Benjamin ;
Meng, Yan ;
Palmer, Cameron D. ;
Esko, Tonu ;
Winckler, Wendy ;
Hirschhorn, Joel N. ;
Kellis, Manolis ;
MacArthur, Daniel G. ;
Getz, Gad ;
Shabalin, Andrey A. ;
Li, Gen ;
Zhou, Yi-Hui ;
Nobel, Andrew B. ;
Rusyn, Ivan ;
Wright, Fred A. ;
Lappalainen, Tuuli ;
Ferreira, Pedro G. ;
Ongen, Halit ;
Rivas, Manuel A. ;
Battle, Alexis ;
Mostafavi, Sara ;
Monlong, Jean ;
Sammeth, Michael ;
Mele, Marta ;
Reverter, Ferran ;
Goldmann, Jakob M. ;
Koller, Daphne ;
Guigo, Roderic ;
McCarthy, Mark I. ;
Dermitzakis, Emmanouil T. ;
Gamazon, Eric R. ;
Im, Hae Kyung ;
Konkashbaev, Anuar ;
Nicolae, Dan L. ;
Cox, Nancy J. ;
Flutre, Timothee ;
Wen, Xiaoquan ;
Stephens, Matthew .
SCIENCE, 2015, 348 (6235) :648-660
[8]   Resistance to BRAF inhibitors induces glutamine dependency in melanoma cells [J].
Baenke, Franziska ;
Chaneton, Barbara ;
Smith, Matthew ;
Van Den Broek, Niels ;
Hogan, Kate ;
Tang, Haoran ;
Viros, Amaya ;
Martin, Matthew ;
Galbraith, Laura ;
Girotti, Maria R. ;
Dhomen, Nathalie ;
Gottlieb, Eyal ;
Marais, Richard .
MOLECULAR ONCOLOGY, 2016, 10 (01) :73-84
[9]   Integrated genomic characterization of IDH1-mutant glioma malignant progression [J].
Bai, Hanwen ;
Harmanci, Akdes Serin ;
Erson-Omay, E. Zeynep ;
Li, Jie ;
Coskun, Sueleyman ;
Simon, Matthias ;
Krischek, Boris ;
Ozduman, Koray ;
Omay, S. Buelent ;
Sorensen, Eric A. ;
Turcan, Sevin ;
Bakirciglu, Mehmet ;
Carrion-Grant, Geneive ;
Murray, Phillip B. ;
Clark, Victoria E. ;
Ercan-Sencicek, A. Gulhan ;
Knight, James ;
Sencar, Leman ;
Altinok, Selin ;
Kaulen, Leon D. ;
Guelez, Burcu ;
Timmer, Marco ;
Schramm, Johannes ;
Mishra-Gorur, Ketu ;
Henegariu, Octavian ;
Moliterno, Jennifer ;
Louvi, Angeliki ;
Chan, Timothy A. ;
Tannheimer, Stacey L. ;
Pamir, M. Necmettin ;
Vortmeyer, Alexander O. ;
Bilguvar, Kaya ;
Yasuno, Katsuhito ;
Guenel, Murat .
NATURE GENETICS, 2016, 48 (01) :59-+
[10]   ATP citrate lyase is an important component of cell growth and transformation [J].
Bauer, DE ;
Hatzivassiliou, G ;
Zhao, FP ;
Andreadis, C ;
Thompson, CB .
ONCOGENE, 2005, 24 (41) :6314-6322