Clonal Heterogeneity Promotes Metabolite Exchange, to Support Pancreatic Tumors

A principal barrier to treatment of pancreatic cancer is the densely fibrotic tumor microenvironment, its high interstitial pressure acts to collapse blood vessels and impair the delivery of chemotherapy. This lack of functional vasculature limits nutrient availability within the tumor, causing cancer cells to develop numerous metabolic adaptations to allow for proliferation in nutrient austere conditions.

The metabolic profiles of a series of clonal cell lines derived from a single pancreatic tumor, were found to be clustered into two distinct groups.

These groups demonstrated differential sensitivities to inhibitors of mitochondrial metabolism, and the growth of sensitive clones were rescued through co-culture with insensitive cells. Chris Halbrook’s team identified this is mediated by exchanged asparagine, released by insensitive cells. Conversely, the use of asparaginase to degrade asparagine sensitizes pancreatic ductal adenocarcinoma tumors to mitochondrial inhibition.

Key webinar discussion topics include:

• How clonal heterogeneity extends to metabolism

• Ascertaining if cancer cell growth can be supported by metabolic crosstalk

• How degradation of asparagine enhances mitochondrial inhibition

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