Cabozantinib and dasatinib synergize to induce tumor regression in non-clear cell renal cell carcinoma
Hui-Wen Lue, Daniel S. Derrick, Soumya Rao, Ahna Van Gaest, Larry C. Cheng, Jennifer Podolak, Samantha Lawson, Changhui Xue, Devin Garg, Ralph E. White, Christopher W. Ryan, Justin M. Drake, Anna Ritz, Laura M. Heiser, George Thomas
Abstract
. Transcriptional and phosphoproteomic profiling reveals that the combination converges to downregulate the MAPK-ERK signaling pathway, a result not predicted by single-agent analysis alone. Correspondingly, the addition of a MEK inhibitor synergizes with either dasatinib or cabozantinib to increase its efficacy. This study, by using approved, clinically relevant drugs, provides the rationale for the design of effective combination treatments in NCCRCC that can be rapidly translated to the clinic.
Topics & Concepts
CabozantinibDasatinibCancer researchRenal cell carcinomaMedicineMAPK/ERK pathwayClear cell renal cell carcinomaProto-oncogene tyrosine-protein kinase SrcDownregulation and upregulationOncologyPharmacologyKinaseInternal medicineBiologyReceptorImatinibCell biologyGeneMyeloid leukemiaBiochemistryRenal cell carcinoma treatmentFerroptosis and cancer prognosisCancer Genomics and Diagnostics