Metabotyping Nutrient Deprivation Response in Cancer Therapy

Cancer cells are often attributed as deadly survivors. They adapt to their environment and make use of all available resources to maintain their growth and proliferation. One of the key features of cancer cells is their ability to adapt their metabolism to available nutrients and use them to create building blocks and energy needed for proliferation. Based on the genetic background and on the nutrient availability in the microenviroment, cancer cells can reprogram their metabolism in different ways and this might make them vulnerable to treatments that target specific metabolic pathways. One such treatment is nutrient restriction, which can be achieved through fasting (complete nutrient restriction) or diets that are restricted in specific nutrients. Researchers have already shown that when combined, nutrient restriction can increase the efficacy of a number of anti-cancer drugs. However, we still dont know which combinations of drugs and nutrient restriction strategies are most effective, and it is yet unknown which patients will respond to such treatments. Therefore, to use nutrient restriction as an additional treatment for patients, we first need to understand how it affects different types of cancer cells, since not all types of cancers respond the same way. The main goals of this project are to identify the most effective combinations of nutrient restriction and anti-cancer drugs for breast cancer, as well as to categorize cancer cells as responders and non- responders to these combination treatments. To investigate this, we will conduct tests on various breast cancer cell lines using different standard drugs and conditions that mimic either a nutrient-rich or nutrient-restricted microenvironment. We will observe how different breast cancer cells respond to these combination treatments. Furthermore, using advanced metabolomics technology, we will analyse the metabolic traits of these cells to understand their energy production and response to treatment. Finally, we will assess how selected cell lines respond to nutrient restriction in animal models that mimic the natural environment within the body. Ultimately, this information could help predict which patients with breast cancer might benefit from nutrient restriction as an additional therapy alongside standard therapy. This project aims to provide valuable insights into the potential and specificity of using nutrient restriction alongside standard anti-cancer treatments. The ultimate goal is to create a personalized approach for treating cancers that are currently resistant to available treatments. Moreover, by studying how cancer cells adapt to nutrient restriction, we might uncover new weaknesses that can be targeted to enhance the effectiveness and specificity of treatments against cancer.