The breast cancer treatment geldanamycin, which works by attacking a protein associated with the spread of breast cancer, has shown potential in a lab-based study for degrading a different protein tied to blood vessel growth—a key to expanding the drug’s use against other forms of cancer.
"This is one of the big problems in cancer: how can we stop the tumor growing and spreading through these blood vessel networks?" the study’s corresponding author, Sreenivasan Ponnambalam, Ph.D., reader in human disease biology in the University of Leeds' Faculty of Biological Sciences, said in a statement. “This [the study] is potentially very significant because tumors secrete substances that stimulate blood vessels to develop around them, forming networks that supply nutrients and provide pathways for spread around the body.”
The two-year Wellcome Trust-funded study involved researchers at the University of Leeds and University College London. Results from the study were published in the journal PLOS ONE.
Dr. Ponnambalam said geldanamycin is an alternative to VEGFR2, which also stops blood vessel growth, albeit by attacking directly the membrane protein, but also has serious side-effects because proteins in the membrane walls of blood vessels control blood pressure and carry out other important work.
Based on experiments with human cells and animal models, the lab study found that geldanamycin indirectly triggered the clearance of the VEGFR2 protein by activating a cellular quality-control system that breaks down many proteins. While that system degrades VEGFR2 relatively slowly, the drug accelerates the process, preventing activation of the protein and inappropriate new blood vessel formation.