PD Dr. Kruthof-de Julio’s lab focuses on developing and applying tools for precision medicine. Two main areas of interest are Prostate and Bladder cancer.
Prostate cancer (PCa) is the most common cancer and the second leading cause of cancer-associated death in men (Centers for Disease Control and Prevention, 2014). Although PCa can be effectively treated in its early stages with surgery and androgen deprivation therapy, the cancer becomes castration resistant and refractory to available therapies in a significant fraction of patients. Castration resistance PCa (CRPC) is thought to arise due to pre-existing stem cell-like PCa cells that survive androgen-deprivation therapy (castration) in a dormant state and then re-initiate tumor growth and metastasis. Therefore, it is critical to identify and target signaling pathways that fuel these cells and drive the castration resistant stage of the disease associated with metastasis and poor patient survival.
Bladder cancer is the fifth most common cancer in the Western world. UCB presents either as non-muscle-invasive (NMIBC) or as muscle-invasive carcinoma (MIBC). NMIBC proliferates continuously but rarely progresses or forms metastasis. It, however, frequently recurs within few months (50-70%). Acquisition of p53 or RB1 mutations can lead to genetic instability and progression to MIBC although this happens rarely (15%). On the other hand, MIBC is genetically instable and acquires further mutations that affect cell/cell and cell/stroma interactions. This leads to an invasive phenotype and allows the tumor metastasize, resulting in very low survival rate of < 50%. By combining conditional mouse models, organoid culture (human and mouse), organoid on CHIP, genomics and metabolomics we aim to characterize the molecular pathways that are associated with therapy resistance and develop novel therapeutics that tackle the resistant disease.