Inhibition of FGF receptor blocks adaptive resistance to RET inhibition in CCDC6-RET-rearranged thyroid cancer.

Renuka Raman¹, Jacques A Villefranc¹, Timothy M Ullmann¹, Jessica Thiesmeyer¹, Viviana Anelli¹, Jun Yao¹, James R Hurley², Chantal Pauli³, Rohan Bareja⁴, Kenneth Wha Eng⁴, Princesca Dorsaint⁴, David C Wilkes⁴, Shaham Beg⁵, Sarah Kudman⁵, Reid Shaw⁶, Michael Churchill⁶, Adnan Ahmed⁷, Laurel Keefer⁸, Ian Misner⁸, Donna Nichol⁸, Naveen Gumpeni⁹, Theresa Scognamiglio⁵, Mark A Rubin¹⁰, Carla Grandori⁶, James Patrick Solomon⁵, Wei Song⁵, Juan Miguel Mosquera⁵, Noah Dephoure^7,11, Andrea Sboner^4,5,11, Olivier Elemento^4,11, Yariv Houvras^1,2,11

¹Department of Surgery, Weill Cornell Medical College, New York, NY.

²Department of Medicine, Weill Cornell Medical College, New York, NY.

³Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland.

⁴The Caryl and Israel Englander Institute for Precision Medicine and the Institute for Computational Biomedicine, Weill Cornell Medical College, New York, NY.

⁵Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY.

⁶SEngine Precision Medicine, Seattle, WA.

⁷Department of Biochemistry, Weill Cornell Medical College, New York, NY.

⁸Personal Genome Diagnostics, Inc., Baltimore, MD.

⁹Department of Radiology, Weill Cornell Medical College, New York, NY.

¹⁰Bern Center for Precision Medicine, University of Bern, Bern, Switzerland.

¹¹Sandra and Edward Meyer Cancer Center, Weill Cornell Medical College, New York, NY.

PubMed PMC DOI PDF

Abstract

Genetic alterations in RET lead to activation of ERK and AKT signaling and are associated with hereditary and sporadic thyroid cancer and lung cancer. Highly selective RET inhibitors have recently entered clinical use after demonstrating efficacy in treating patients with diverse tumor types harboring RET gene rearrangements or activating mutations. In order to understand resistance mechanisms ari…

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