This seminar will describe the development of a phenotypic drug screen to identify novel small molecules that alter cell metabolism and are selectively toxic to cancer.
This seminar will describe the development of a phenotypic drug screen to identify novel small molecules that alter cell metabolism and are selectively toxic to cancer cells. The basis for this drug screen was the knowledge that most genetic aberrations that initiate and promote cancer development in one way or another regulate cell metabolism. Not surprisingly, dysregulated metabolism is recognised as a hallmark of cancer and potential vulnerability by which to target cancer cells. From this screen a lead molecule was discovered that displays better cancer cell-specific toxicity than many frontline chemotherapy agents and molecules known to target cancer metabolism. Metabolomics and metabolic flux experiments helped determine how this molecule induces cancer cell death and selective toxicity. Working alongside medicinal chemists has led to the development of new molecules, with improved pharmacokinetics and oral bioavailability that may facilitate translational into the clinic.
Dr Frances Byrne completed her PhD at the Children’s Cancer Institute (UNSW) where she investigated the role of microtubule regulatory proteins in cancer cell drug resistance and metastasis. In 2012 she started her postdoc at the University of Virginia (USA) where she began her research on cancer cell metabolism in the laboratory of Dr Kyle Hoehn. There she revealed a new role for a lesser-known glucose transporter, GLUT6, in cancer cell biology. Since returning to Australia in 2014, Dr Byrne has created and phenotyped the first CRISPR-Cas9 GLUT6 knockout mouse and developed a new mouse model of obesity-related endometrial cancer that mimics the initiation and progression of this common cancer in women. Dr Byrne is currently a Cancer Institute NSW Early Career Fellow whose research is focussed on developing therapeutic strategies to target cancer cell metabolism and investigating how diet and obesity contribute to cancer development.