2024 World Conference on Lung Cancer (WCLC) - Posters-P3.02F.04 Investigating the Role of Lactate Import and Metabolism in Non-Small Cell Lung Cancer

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The study, conducted by researchers at the University of Chicago, investigates the metabolic role of lactate in non-small cell lung cancer (NSCLC). Historically regarded as a waste product, lactate is redefined in this research as a crucial fuel for NSCLC cells, specifically in the H1299 cell line, which uses lactate for the tricarboxylic acid (TCA) cycle and amino acid synthesis. The study highlights that lactate is the preferred energy source over glucose in these cancer cells. <br /><br />Pharmacological inhibition of the lactate transporter MCT1 with AZD3965 significantly reduces lactate uptake into the TCA cycle in vitro. This inhibition leads to altered glucose metabolism, suggesting MCT1's pivotal role in lactate utilization. In vivo, increased lactate uptake correlates with poorer prognosis and survival in NSCLC patients.<br /><br />The methodology includes comparing multiple growth media to better simulate in vivo conditions, showing that media composition affects lactate metabolism in cultured cancer cells. Different labeling of isotopes ([U13C]-glucose and 12C-lactate) further delineates metabolic pathways, analyzed by gas chromatography-mass spectrometry (GC-MS).<br /><br />Patient-derived xenografts (PDXs) offer insights into tumor lactate metabolism, mimicking patient tumor characteristics and spontaneous metastasis in immunodeficient mice. The study's findings stress the importance of creating more physiological models to understand cancer metabolism accurately.<br /><br />The conclusions underscore the need for deeper exploration of glucose's metabolic role under basal conditions, and further understanding of metabolic changes during metastasis, progression, and treatment resistance in NSCLC. The research demonstrates that targeting lactate import via MCT1 may be a potential therapeutic strategy in combating NSCLC.

Asset Subtitle

Robert Cameron

Meta Tag

Speaker Robert Cameron

Topic Tumor Biology – Preclinical Biology

Keywords

lactate

NSCLC

MCT1

metabolism

TCA cycle

AZD3965

glucose

xenografts

cancer cells

therapeutic strategy