Project Details
Projekt
Investigation of a novel microdevice for drug evaluation and discovery in non-clear cell renal cell carcinoma
Applicant
Dr. Clara Steiner
Subject Area
Reproductive Medicine, Urology
Term
since 2024
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 542998520
Within kidney cancer, most prior clinical studies and biomarker analyses have focused on clear cell renal cell carcinoma (ccRCC). There is limited clinical data to guide the treatment of non-clear cell RCCs (nccRCC), which account for approximately 25% of all renal cell carcinomas (RCC). Therefore, current treatment paradigms for nccRCC are largely extrapolated from ccRCC therapies and do not reflect underlying tumor biology. Due to the small number of patients and the histologic heterogeneity of nccRCC, conducting clinical trials is very challenging. Furthermore, there are several different combinations available for first-line therapy in metastatic RCC and treatment decisions are mostly based on experience and provider preference. To date, there are no established biomarkers that can be used in clinical practice to guide personalized treatment decisions.To address this clinical unmet need, we will investigate an implantable microdevice (IMD) for patients with nccRCC who are planned for resection of the primary tumor or metastases as part of their clinical care. The microdevices were developed by investigators of Brigham and Women’s Hospital and Dana-Farber Cancer Institute in Boston and are the size of a grain of rice. By placing the IMD within a target tumor using a standard interventional deployment needle, up to 20 different drugs and/or combinations could be administered locally to distinct areas of the tumor. Consequently, disease response to multiple therapies could be assessed in vivo. Using this method, we aim to establish a way to test the effectiveness of drugs without exposing patients to systemic toxicity, because the drugs are only delivered to the tumor microenvironment and not applied systemically. Therefore, even novel therapeutic therapies addressing new molecular targets in non-clear cell RCC subtypes could be tested in vivo. We aim to show safety and feasibility of microdevice implantation in nccRCC, evaluate the immunohistochemical correlation of treatment response and study the effects of drugs on the tumor immune microenvironment. Performing a diagnostic assessment of each drug effect, we will generate tumor drug response profiles for a range of drugs in nccRCC based on a patient’s individual tumor biology. We also seek to identify tumor features that predict response to therapy and could be used as predictive biomarkers in clinical use. The lack of individualized treatment algorithms leads to the administration of ineffective substances costing time for the patient, resources in the health care system and leading to potential side effects. Establishing a method for simultaneously evaluating the anti-tumoral effects of several therapeutic options in a short amount of time would bring us one step closer to individualized tumor therapy for patients with nccRCC.
DFG Programme
WBP Fellowship
International Connection
USA
