Targeting Strategies for Glucose Metabolic Pathways and T Cells in Colorectal Cancer.

Curr Cancer Drug Targets 2019 ;19(7):534-550

Department of Medicine, Jiangsu University, Zhenjiang City, Jiangsu Province 212001, China.

Colorectal cancer is a heterogeneous group of diseases that result from the accumulation of different sets of genomic alterations, together with epigenomic alterations, and it is influenced by tumor-host interactions, leading to tumor cell growth and glycolytic imbalances. This review summarizes recent findings that involve multiple signaling molecules and downstream genes in the dysregulated glycolytic pathway. This paper further discusses the role of the dysregulated glycolytic pathway in the tumor initiation, progression and the concomitant systemic immunosuppression commonly observed in colorectal cancer patients. Moreover, the relationship between colorectal cancer cells and T cells, especially CD8+ T cells, is discussed, while different aspects of metabolic pathway regulation in cancer cell proliferation are comprehensively defined. Furthermore, this study elaborates on metabolism in colorectal cancer, specifically key metabolic modulators together with regulators, glycolytic enzymes, and glucose deprivation induced by tumor cells and how they inhibit T-cell glycolysis and immunogenic functions. Moreover, metabolic pathways that are integral to T cell function, differentiation, and activation are described. Selective metabolic inhibitors or immunemodulation agents targeting these pathways may be clinically useful to increase effector T cell responses for colorectal cancer treatment. However, there is a need to identify specific antigens using a cancer patient-personalized approach and combination strategies with other therapeutic agents to effectively target tumor metabolic pathways.

Download full-text PDF

Source
http://dx.doi.org/10.2174/1568009618666181015150138DOI Listing
January 2019
11 Reads

Publication Analysis

Top Keywords

colorectal cancer
24
metabolic pathways
12
dysregulated glycolytic
8
cancer
8
glycolytic pathway
8
colorectal
6
metabolic
6
cells
5
systemic immunosuppression
4
glucose deprivation
4
increase effector
4
effector cell
4
progression concomitant
4
immunosuppression commonly
4
concomitant systemic
4
pathways clinically
4
cells inhibit
4
observed colorectal
4
commonly observed
4
cancer patients
4

References

(Supplied by CrossRef)

Song L.L. et al.
World J Gastrointest Oncol 2016

Siegel R. et al.
CA Cancer J Clin 2013

Fearon E.R. et al.
Cell 1990

Cunningham D. et al.
Lancet 2010

Sameer A.S. et al.
Front Oncol 2013

Jiménez B. et al.
J Proteome Res 2013

Williams M.D. et al.
Anal Bioanal Chem 2015

Graziano F. et al.
Pharmacogenomics J 2017

Yeh C.S. et al.
Oncol Rep 2008

Bi X. et al.
Mol Cell Proteomics 2006

Brown D.G. et al.
Cancer Metab 2016

Similar Publications