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
Live question and answers
Dr. Chris Halbrook
Department of Molecular Biology and Biochemistry
University of California Irvine
Dr. Chris Halbrook is an Assistant Professor in the Department of Molecular Biology and Biochemistry at the University of California Irvine.
His research focuses on understanding the metabolic mechanisms driving cancer cell proliferation in the tumor microenvironment, with the goal of developing new therapy options.
This work has identified several mechanisms of metabolic crosstalk with functional consequences on pancreatic tumor growth, chemoresistance, and immune suppression.