Defining the critical building blocks
Cancer cells must produce large amounts of proteins to support proliferation. Protein production is a team effort requiring a variety of molecular players responsible for moving amino acid building blocks into position for assembly. In the protein production line, the enzyme Aminoacyl-tRNA synthetase (ARS) operates like a molecular forklift loading amino acids onto transportation vehicles (tRNAs) which take them to the peptide assembly station. Cancer cannot proliferate if the critical ARS enzyme is inhibited. There are 20 ARSs in the human body, and Dr. Alan Gerber believes that certain ARSs may be critical for cancer proliferation but less so for healthy cells. “Cancer cells could be targeted specifically by reducing the activity of critical ARS enzymes, with limited effects on normal cells,” Dr. Gerber hypothesizes.
Disrupting the critical building blocks
Cancer Center Amsterdam Foundation is funding Dr. Gerber’s research with a new project called ‘Precision targeting of aminoacyl-tRNA-synthetases in cancer’. Dr. Gerber and his team plan to reduce the expression of each ARS enzyme independently in brain cancer cells and normal cells to identify which ARS enzymes are most important for cancer growth. “We will then assess if the identified ARS can be targeted efficiently with already available drugs,” explains Dr. Gerber. In the future, if sensitivity signatures of cancer protein production can be predicted based on gene expression profiles, the signatures of a patient’s tumor could guide the selection of drug combinations to efficiently kill cancer cells without affecting normal cells.
tRNA ligase
Dr. Alan Gerber, lead principal investigator
For more information, please contact Dr. Alan Gerber
People involved at Cancer Center Amsterdam – Amsterdam UMC:
Dr. Alan Gerber, Neurosurgery
Chantal Scheepbouwer, Neurosurgery
Dr. Elisa Giovannetti, Medical Oncology
Dr. Rob Wolthuis, Human Genetics
Prof. Tom Würdinger, Neurosurgery
Text by Lynita Howie