Structural and functional regulation of lactate dehydrogenase-A in cancer.

Abstract:

:Dysregulated metabolism is one of the hallmarks of cancer. Under normal physiological conditions, ATP is primarily generated by oxidative phosphorylation. Cancers commonly undergo a dramatic shift toward glycolysis, despite the presence of oxygen. This phenomenon is known as the Warburg effect, and requires the activity of LDHA. LDHA converts pyruvate to lactate in the final step of glycolysis and is often upregulated in cancer. LDHA inhibitors present a promising therapeutic option, as LDHA blockade leads to apoptosis in cancer cells. Despite this, existing LDHA inhibitors have shown limited clinical efficacy. Here, we review recent progress in LDHA structure, function and regulation as well as strategies to target this critical enzyme.

journal_name

Future Med Chem

authors

Woodford MR,Chen VZ,Backe SJ,Bratslavsky G,Mollapour M

doi

10.4155/fmc-2019-0287

subject

Has Abstract

pub_date

2020-03-01 00:00:00

pages

439-455

issue

5

eissn

1756-8919

issn

1756-8927

journal_volume

12

pub_type

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