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Pyruvate Kinase M2: a Metabolic Bug in Re-Wiring the Tumor Microenvironment

Pyruvate Kinase M2: a Metabolic Bug in Re-Wiring the Tumor Microenvironment Metabolic reprogramming is a newly emerged hallmark of cancer attaining a recent consideration as an essential factor for the progression and endurance of cancer cells. A prime event of this altered metabolism is increased glucose uptake and discharge of lactate into the cells surrounding constructing a favorable tumor niche. Several oncogenic factors help in promoting this consequence including, pyruvate kinase M2 (PKM2) a rate-limiting enzyme of glycolysis in tumor metabolism via exhibiting its low pyruvate kinase activity and nuclear moon-lightening functions to increase the synthesis of lactate and macromolecules for tumor proliferation. Not only its role in cancer cells but also its role in the tumor microenvironment cells has to be understood for developing the small molecules against it which is lacking with the literature till date. Therefore, in this present review, the role of PKM2 with respect to various tumor niche cells will be clarified. Further, it highlights the updated list of therapeutics targeting PKM2 pre-clinically and clinically with their added limitations. This upgraded understanding of PKM2 may provide a pace for the reader in developing chemotherapeutic strategies for better clinical survival with limited resistance. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Cancer Microenvironment Springer Journals

Pyruvate Kinase M2: a Metabolic Bug in Re-Wiring the Tumor Microenvironment

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Publisher
Springer Journals
Copyright
Copyright © 2019 by Springer Nature B.V.
Subject
Biomedicine; Cancer Research; Oncology; Immunology; Cell Biology; Biochemistry, general; Biomedicine, general
ISSN
1875-2292
eISSN
1875-2284
DOI
10.1007/s12307-019-00226-0
Publisher site
See Article on Publisher Site

Abstract

Metabolic reprogramming is a newly emerged hallmark of cancer attaining a recent consideration as an essential factor for the progression and endurance of cancer cells. A prime event of this altered metabolism is increased glucose uptake and discharge of lactate into the cells surrounding constructing a favorable tumor niche. Several oncogenic factors help in promoting this consequence including, pyruvate kinase M2 (PKM2) a rate-limiting enzyme of glycolysis in tumor metabolism via exhibiting its low pyruvate kinase activity and nuclear moon-lightening functions to increase the synthesis of lactate and macromolecules for tumor proliferation. Not only its role in cancer cells but also its role in the tumor microenvironment cells has to be understood for developing the small molecules against it which is lacking with the literature till date. Therefore, in this present review, the role of PKM2 with respect to various tumor niche cells will be clarified. Further, it highlights the updated list of therapeutics targeting PKM2 pre-clinically and clinically with their added limitations. This upgraded understanding of PKM2 may provide a pace for the reader in developing chemotherapeutic strategies for better clinical survival with limited resistance.

Journal

Cancer MicroenvironmentSpringer Journals

Published: Jun 10, 2019

References