Sunitinib induces early histomolecular changes in a subset of renal cancer cells that contribute to resistance

• DOI: 10.1096/fj.201800596r
• Publication Date: 2018-08-27T17:40:31Z
• Authors: Zsuzsanna Lichner; Rola Saleeb; Henriett Butz; Qiang Ding; Roy Nofech-Mozes; Sara Riad; Mina Farag; Amir K. Varkouhi; Claudia C. dos Sa...; András Kapus; George M. Yousef
• Keywords: Mice, Inbred BALB C; 0303 health sciences; Stem Cells; Antineoplastic Agents; Xenograft Model Antitumor Assays; Kidney Neoplasms; 3. Good health; Mice; 03 medical and health sciences; R1 Medicine (General) / orvostudomány általában; Drug Resistance, Neoplasm; Cell Line, Tumor; Spheroids, Cellular; Biomarkers, Tumor; Sunitinib; Animals; Humans; Female; Carcinoma, Renal Cell; Cell Proliferation

ABSTRACT Sunitinib is the standard‐of‐care, first‐line treatment for advanced renal cell carcinoma (RCC). Characteristics of treatment‐resistant RCC have been described; however, complex tumor adaptation mechanisms obstruct identification significant operators in resistance. We hypothesized that resistance a late manifestation early, treatment‐induced histomolecular alterations; therefore, studying early drug response may identify drivers describe an epithelioid growth pattern xenografts, which emerges sunitinib‐sensitive tumors and augmented during This modality molecularly morphologically related to spheroids advance vitro treatment. Based on time‐lapse microscopy, mRNA microRNA screening, behavior‐related characteristics, we propose spheroid adherent patterns differentially respond sunitinib. Gene expression analysis indicated sunitinib promoted formation, provided selective survival advantage under Functional studies confirm E‐cadherin key contributor cells In summary, suggest sunitinib‐resistant exist treatment‐sensitive are histologically identifiable.—Lichner, Z., Saleeb, R., Butz, H., Ding, Q., Nofech‐Mozes, Riad, S., Farag, M., Varkouhi, A. K., dosSantos, C. C., Kapus, A., Yousef, G. M. induces changes subset cancer contribute FASEB J. 33, 1347–1359 (2019). www.fasebj.org