A combinatorial strategy for treating KRAS-mutant lung cancer

Nature

Volumn 534, Issue 7609, 2016, Pages 647-651

  Manchado, Eusebio ^a   Weissmueller, Susann ^a,b   Morris, John P ^a   Chen, Chi Chao ^a,c   Wullenkord, Ramona ^a   Lujambio, Amaia ^a,d   De Stanchina, Elisa ^a   Poirier, John T ^a   Gainor, Justin F ^e   Corcoran, Ryan B ^e   Engelman, Jeffrey A ^e   Rudin, Charles M ^a   Rosen, Neal ^a   Lowe, Scott W ^a,f  

^a MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

^b Howard Hughes Medical Institute Cold Spring Harbor Laboratory Cold Spring Harbor   (United States)

^c Weill Cornell Graduate School of Biomedical Sciences   (United States)

^d MOUNT SINAI SCHOOL OF MEDICINE   (United States)

^e HARVARD MEDICAL SCHOOL   (United States)

^f HOWARD HUGHES MEDICAL INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

FIBROBLAST GROWTH FACTOR RECEPTOR 1; FIBROBLAST GROWTH FACTOR RECEPTOR 2; MITOGEN ACTIVATED PROTEIN KINASE; PONATINIB; SHORT HAIRPIN RNA; TRAMETINIB; TUMOR MARKER; ANTINEOPLASTIC AGENT; FGFR1 PROTEIN, HUMAN; IMIDAZOLE DERIVATIVE; KRAS PROTEIN, HUMAN; KRAS2 PROTEIN, MOUSE; MITOGEN ACTIVATED PROTEIN KINASE KINASE; MUTANT PROTEIN; PROTEIN P21; PYRIDAZINE DERIVATIVE; PYRIDONE DERIVATIVE; PYRIMIDINONE DERIVATIVE;

ALTERNATIVE AGRICULTURE; BIOMARKER; CANCER; CELL; INHIBITION; INHIBITOR; MUTATION; PROTEIN; TUMOR;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CANCER COMBINATION CHEMOTHERAPY; CANCER REGRESSION; CELL DEATH; CLINICAL ARTICLE; COLON CANCER CELL LINE; CONTROLLED STUDY; DRUG EFFECT; DRUG IDENTIFICATION; DRUG INHIBITION; DRUG SCREENING; DRUG SENSITIVITY; FEMALE; GENE MUTATION; GENE REPRESSION; GENETIC SCREENING; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; LUNG CANCER; MOUSE; NONHUMAN; ONCOGENE K RAS; PANCREATIC CANCER CELL LINE; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; TREATMENT PLANNING; TUMOR VOLUME; TUMOR XENOGRAFT; WILD TYPE; ADENOCARCINOMA; ANIMAL; ANTAGONISTS AND INHIBITORS; CELL PROLIFERATION; COLON TUMOR; DISEASE MODEL; DRUG EFFECTS; DRUG RESISTANCE; ENZYME ACTIVATION; FEEDBACK SYSTEM; GENETICS; LUNG NEOPLASMS; METABOLISM; MUTATION; PANCREAS TUMOR; PATHOLOGY; PHOSPHORYLATION; SIGNAL TRANSDUCTION;

ADENOCARCINOMA; ANIMALS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CELL DEATH; CELL PROLIFERATION; COLONIC NEOPLASMS; DISEASE MODELS, ANIMAL; DRUG RESISTANCE, NEOPLASM; DRUG SCREENING ASSAYS, ANTITUMOR; ENZYME ACTIVATION; FEEDBACK, PHYSIOLOGICAL; FEMALE; HUMANS; IMIDAZOLES; LUNG NEOPLASMS; MAP KINASE SIGNALING SYSTEM; MICE; MITOGEN-ACTIVATED PROTEIN KINASE KINASES; MUTANT PROTEINS; MUTATION; PANCREATIC NEOPLASMS; PHOSPHORYLATION; PROTO-ONCOGENE PROTEINS P21(RAS); PYRIDAZINES; PYRIDONES; PYRIMIDINONES; RECEPTOR, FIBROBLAST GROWTH FACTOR, TYPE 1; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84979497068     PISSN: 00280836     EISSN: 14764687     Source Type: Journal    
DOI: 10.1038/nature18600     Document Type: Article

References (36)

1. Downward, J. Targeting RAS signalling pathways in cancer therapy. Nature Rev. Cancer 3, 11-22 (2003).
2. Ostrem, J. M., Peters, U., Sos, M. L., Wells, J. A. & Shokat, K. M. K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions. Nature 503, 548-551 (2013).
3. Barbie, D. A. et al. Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1. Nature 462, 108-112 (2009).
4. Scholl, C. et al. Synthetic lethal interaction between oncogenic KRAS dependency and STK33 suppression in human cancer cells. Cell 137, 821-834 (2009).
5. Luo, J. et al. A genome-wide RNAi screen identifies multiple synthetic lethal interactions with the Ras oncogene. Cell 137, 835-848 (2009).
6. Stephen, A. G., Esposito, D., Bagni, R. K. & McCormick, F. Dragging ras back in the ring. Cancer Cell 25, 272-281 (2014).
7. Cox, A. D., Fesik, S. W., Kimmelman, A. C., Luo, J. & Der, C. J. Drugging the undruggable RAS: mission possible? Nature Rev. Drug Discov. 13, 828-851 (2014).
8. Lito, P., Rosen, N. & Solit, D. B. Tumor adaptation and resistance to RAF inhibitors. Nature Med. 19, 1401-1409 (2013).
9. Samatar, A. A. & Poulikakos, P. I. Targeting RAS-ERK signalling in cancer: promises and challenges. Nature Rev. Drug Discov. 13, 928-942 (2014).
10. Lito, P. et al. Disruption of CRAF-mediated MEK activation is required for effective MEK inhibition in KRAS mutant tumors. Cancer Cell 25, 697-710 (2014).
11. Sun, C. et al. Intrinsic resistance to MEK inhibition in KRAS mutant lung and colon cancer through transcriptional induction of ERBB3. Cell Reports 7, 86-93 (2014).
12. Zuber, J. et al. Toolkit for evaluating genes required for proliferation and survival using tetracycline-regulated RNAi. Nature Biotechnol. 29, 79-83 (2011).
13. Manning, G., Whyte, D. B., Martinez, R., Hunter, T. & Sudarsanam, S. The protein kinase complement of the human genome. Science 298, 1912-1934 (2002).
14. Morris, E. J. et al. Discovery of a novel ERK inhibitor with activity in models of acquired resistance to BRAF and MEK inhibitors. Cancer Discov. 3, 742-750 (2013).
15. Lee, H. J. et al. Drug resistance via feedback activation of Stat3 in oncogeneaddicted cancer cells. Cancer Cell 26, 207-221 (2014).
16. Nazarian, R. et al. Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation. Nature 468, 973-977 (2010).
17. Villanueva, J. et al. Acquired resistance to BRAF inhibitors mediated by a RAF kinase switch in melanoma can be overcome by cotargeting MEK and IGF-1R/ PI3K. Cancer Cell 18, 683-695 (2010).
18. Corcoran, R. B. et al. EGFR-mediated re-activation of MAPK signaling contributes to insensitivity of BRAF mutant colorectal cancers to RAF inhibition with vemurafenib. Cancer Discov. 2, 227-235 (2012).
19. Prahallad, A. et al. Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR. Nature 483, 100-103 (2012).
20. Duncan, J. S. et al. Dynamic reprogramming of the kinome in response to targeted MEK inhibition in triple-negative breast cancer. Cell 149, 307-321 (2012).
21. Kouhara, H. et al. A lipid-anchored Grb2-binding protein that links FGFreceptor activation to the Ras/MAPK signaling pathway. Cell 89, 693-702 (1997).
22. Gozgit, J. M. et al. Ponatinib (AP24534), a multitargeted pan-FGFR inhibitor with activity in multiple FGFR-amplified or mutated cancer models. Mol. Cancer Ther. 11, 690-699 (2012).
23. Guagnano, V. et al. Discovery of 3-(2, 6-dichloro-3, 5-dimethoxy-phenyl)-1-{6-[4-(4-ethyl-piperazin-1-yl)-phenylamino]-pyrimidin-4-yl}-1-methyl-urea (NVP-BGJ398), a potent and selective inhibitor of the fibroblast growth factor receptor family of receptor tyrosine kinase. J. Med. Chem. 54, 7066-7083 (2011).
24. Gavine, P. R. et al. AZD4547: an orally bioavailable, potent, and selective inhibitor of the fibroblast growth factor receptor tyrosine kinase family. Cancer Res. 72, 2045-2056 (2012).
25. Li, F. et al. FGFR-mediated reactivation of MAPK signaling attenuates antitumor effects of imatinib in gastrointestinal stromal tumors. Cancer Discov. 5, 438-451 (2015).
26. Traer, E. et al. Ponatinib overcomes FGF2-mediated resistance in CML patients without kinase domain mutations. Blood 123, 1516-1524 (2014).
27. Jackson, E. L. et al. The differential effects of mutant p53 alleles on advanced murine lung cancer. Cancer Res. 65, 10280-10288 (2005).
28. Shao, D. D. et al. KRAS and YAP1 converge to regulate EMT and tumor survival. Cell 158, 171-184 (2014).
29. Shimizu, T. et al. The clinical effect of the dual-targeting strategy involving PI3K/AKT/mTOR and RAS/MEK/ERK pathways in patients with advanced cancer. Clin. Cancer Res. 18, 2316-2325 (2012).
30. Fellmann, C. et al. Functional identification of optimized RNAi triggers using a massively parallel sensor assay. Mol. Cell 41, 733-746 (2011).
31. Taylor, J., Schenck, I., Blankenberg, D. & Nekrutenko, A. in Current Protocols in Bioinformatics (eds Baxevanis, A. D. et al.) Ch. 10, Unit 10.5 (Wiley, 2007).
32. Chou, T. C. Drug combination studies and their synergy quantification using the Chou-Talalay method. Cancer Res. 70, 440-446 (2010).
33. Poirier, J. T. et al. DNA methylation in small cell lung cancer defines distinct disease subtypes and correlates with high expression of EZH2. Oncogene 34, 5869-5878 (2015).
34. DuPage, M., Dooley, A. L. & Jacks, T. Conditional mouse lung cancer models using adenoviral or lentiviral delivery of Cre recombinase. Nature Protocols 4, 1064-1072 (2009).
35. Huch, M. et al. Unlimited in vitro expansion of adult bi-potent pancreas progenitors through the Lgr5/R-spondin axis. EMBO J. 32, 2708-2721 (2013).
36. Saborowski, M. et al. A modular and flexible ESC-based mouse model of pancreatic cancer. Genes Dev. 28, 85-97 (2014).