JAK2 inhibition sensitizes resistant EGFR-mutant lung adenocarcinoma to tyrosine kinase inhibitors

Author:

Gao Sizhi P.1,Chang Qing1,Mao Ninghui1,Daly Laura A.1,Vogel Robert2,Chan Tyler1,Liu Shu Hui1,Bournazou Eirini1,Schori Erez1,Zhang Haiying3,Red Brewer Monica45,Pao William45,Morris Luc6,Ladanyi Marc78,Arcila Maria7,Manova-Todorova Katia9,de Stanchina Elisa10,Norton Larry111,Levine Ross L.1811,Altan-Bonnet Gregoire2,Solit David181112,Zinda Michael13,Huszar Dennis13,Lyden David31415,Bromberg Jacqueline F.111

Affiliation:

1. Department of Medicine, Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY 10065, USA.

2. Computational Biology Program, MSKCC, New York, NY 10065, USA.

3. Children’s Cancer and Blood Foundation Laboratories, Departments of Pediatrics, Cell and Developmental Biology, Weill Cornell Medical College (WCMC), New York, NY 10021, USA.

4. Division of Hematology/Oncology, Vanderbilt-Ingram Cancer Center (VICC), Nashville, TN 37232, USA.

5. Personalized Cancer Medicine, VICC, Nashville, TN 37232, USA.

6. Department of Surgery, MSKCC, New York, NY 10065, USA.

7. Department of Pathology, MSKCC, New York, NY 10065, USA.

8. Human Oncology and Pathogenesis Program, MSKCC, New York, NY 10065, USA.

9. Molecular Cytology, MSKCC, New York, NY 10065, USA.

10. Antitumor Assessment, MSKCC, New York, NY 10065, USA.

11. WCMC, New York, NY 10021, USA.

12. Metastasis Research Center, MSKCC, New York, NY 10065, USA.

13. Oncology iMED, AstraZeneca, Waltham, MA 02451, USA.

14. Department of Pediatrics, MSKCC, New York, NY 10065, USA.

15. Drukier Institute for Children’s Health, Meyer Cancer Center, WCMC, New York, NY 10021, USA.

Abstract

JAK2 inhibitors increase the abundance of EGFR in lung cancer cells, thereby restoring the efficacy of EGFR inhibitors in resistant tumors.

Funder

NIH

Charles and Marjorie Holloway Foundation

Sussman Family Fund

Lerner Foundation

Astra Zeneca

Manhasset Women's Coalition Against Breast Cancer

New York State USBC Women's Bowling Association

Uniting Against Lung Cancer

Children's Cancer and Blood Foundation

Manning Foundation

Hartwell Foundation

Pediatric Oncology Experimental Therapeutics Investigators Consortium

Stavros S. Niarchos Foundation

Champalimaud Foundation

Nancy C. and Daniel P. Paduano Foundation

Mary Kay Foundation

American Hellenic Educational Progressive Association, 5th District

Malcolm Hewitt Wiener Foundation

George Best Costacos Foundation

National Cancer Institute

Susan G. Komen for the Cure

Physical Sciences-Oncology Centers

Beth C. Tortolani Foundation

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Cell Biology,Molecular Biology,Biochemistry

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