Public summaries of the project:
SPatial Heterogeneity of INtratumoral drug distribution (SPHINx)
Dr. C.W. Menke-van der Houven van Oordt, AmsterdamUMC Location VUmc
Dr. R. Deckers, University Medical Center Utrecht
Prof. A.D.R. Huitema, Netherlands Cancer Institute
Dr. L. Wee, Maastricht University
More and more people are living longer with cancer, or even cured of it, thanks to the development of new and better treatments. Yet there is still a large group of patients in whom these new treatments fail. For effective cancer treatment, drugs must reach all cancer cells in the body. However, tumors have aberrant anatomy and physiology that can interfere with the supply and distribution of drugs. The goal of this project is to use advanced imaging techniques to measure drug distribution and tumor characteristics that determine this drug distribution within the tumor at different length scales. A window-of-opportunity clinical trial will be performed in postmenopausal patients with early ER+ breast cancer, who are scheduled for surgery. During two weeks before surgery, patients will be treated with aromatase inhibitor and CDK4/6 inhibitor. The new knowledge provides a valuable basis for strategies improving drug distribution and ultimately patient outcomes.
Decoding the emerging role of dynamic tRNA gene regulation in cancer and cellular adaptions to changing environments
Prof. F. Van Leeuwen, Netherlands Cancer Institute
Dr A. Gerber, Amsterdam UMC, location VUmc
Protein synthesis in the cell requires a vast amount of resources. It has to be tightly regulated to ensure sufficient number of proteins are made while energy waste is minimized. tRNAs are adaptor molecules that are essential for protein synthesis. They are highly expressed and were initially thought to be regulated in a uniform manner. However, it recently emerged that there is selective regulation of tRNAs to favor the translation of key proteins driving cellular processes such as proliferation, notably in cancer cells. The mechanisms of the non-uniform regulation remain unknown. This knowledge gap is caused by technical hurdles and limited studies on the tRNA production machinery. Gerber and Van Leeuwen are developing innovative technologies to decode the mechanisms of non-uniform of tRNA regulation. The studies will provide insights into how selective tRNA regulation can influence cell growth and survival and uncover a previously untapped trove of potential therapeutic targets.
For more information, contact Alan Gerber or Willemien Menke-van der Houven van Oordt.