Extracellular vesicles mediate interorgan crosstalk during TKI-induced chemotherapy

I am exploring why VEGF-targeted tyrosine kinase inhibitors used in treatment of metastatic renal cell carcinoma drive cardiotoxicity. In vitro, I treated human cardiomyocyte (AC16) and kidney epithelial (HK-2) cell lines with four clinically relevant TKIs at subtherapeutic, therapeutic, and supratherapeutic concentrations. I then quantified autophagy and cell death using fluorescence-activated cell sorting (FACS). My results show that lenvatinib and sorafenib cause marked, dose‑dependent suppression of autophagy in cardiomyocytes, whereas HK‑2 cells maintain very high baseline autophagy and viability, revealing cell‑specific stress buffering and drug‑dependent toxicity patterns. Building on this baseline, I plan to develop transwell co‑culture systems and extracellular vesicle isolation workflows to test whether vesicle cargo serves as a molecular “stress signal” that links cardiac and renal injury during TKI chemotherapy.