Colorectal cancer (CRC) is responsible for causing 900,000 deaths annually. Tyrosine kinase inhibitors (TKIs) have shown promising results preclinically, however many TKIs fail in clinical trials partly due to suboptimal dosing. To address this, this study explored a high-dose short-term (HDST) TKI treatment approach in patient-derived tumour organoids (PDTOs). The study extensively focussed on two TKIs- sunitinib and osimertinib. While high-dose sunitinib failed to improve patient outcomes due to increased toxicity in a phase II clinical trial, osimertinib effectively stopped tumour growth in preclinical models that closely mimicked patient tumours. Moreover, osimertinib accumulated more in these PDTOs as compared to the currently approved drug, regorafenib. High-dose osimertinib as monotherapy seems to be promising for the treatment for metastatic CRC. Alternatively, combining sunitinib with elacridar also seemed to improve the efficacy of this drug in CRC models. Overall, the research highlights new avenues for improving TKI effectiveness in mCRC.
Kirti K. Iyer (1995) completed her degree in Bachelors of Technology in Biotechnology (cum laude, 2017) in India. She moved to The Netherlands to pursue her master’s in Molecular Genetics & Biotechnology from Leiden University. After performing two extensive internships focusing on different types of cancers, she embarked on her Ph.D. journey to improve the efficacy of tyrosine kinase inhibitors (TKIs) in colorectal cancer.