Combination inhibition of PI3K and mTORC1 yields durable remissions in mice bearing orthotopic patient-derived xenografts of HER2-positive breast cancer brain metastases

Nature Medicine

Volumn 22, Issue 7, 2016, Pages 723-726

  Ni, Jing ^a,b   Ramkissoon, Shakti H ^b,c   Xie, Shaozhen ^a,b   Goel, Shom ^a,b   Stover, Daniel G ^b   Guo, Hanbing ^a,b   Luu, Victor ^a,b   Marco, Eugenio ^a   Ramkissoon, Lori A ^b   Kang, Yun Jee ^b   Hayashi, Marika ^b   Nguyen, Quang De ^a   Ligon, Azra H ^c   Du, Rose ^c   Claus, Elizabeth B ^c,d   Alexander, Brian M ^a,c   Yuan, Guo Cheng ^a   Wang, Zhigang C ^a,b   Iglehart, J Dirk ^a,b   Krop, Ian E ^b   Roberts, Thomas M ^a,b   Winer, Eric P ^b   Lin, Nancy U ^b   Ligon, Keith L ^b,c   Zhao, Jean J ^a,b   more..

^a DANA FARBER CANCER INSTITUTE   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

^c BRIGHAM AND WOMEN S HOSPITAL   (United States)

^d YALE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 (4 CHLOROPHENYL) 2,3,9 TRIMETHYL 6H THIENO[3,2 F][1,2,4]TRIAZOLO[4,3 A][1,4]DIAZEPINE 6 ACETIC ACID TERT BUTYL ESTER; BINIMETINIB; BIOLOGICAL MARKER; BUPARLISIB; CASPASE 3; EPIDERMAL GROWTH FACTOR RECEPTOR 2; EVEROLIMUS; INITIATION FACTOR 4E BINDING PROTEIN 1; LAPATINIB; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; MAMMALIAN TARGET OF RAPAMYCIN INHIBITOR; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3 KINASE INHIBITOR; RAPAMYCIN; AMINOPYRIDINE DERIVATIVE; ANTINEOPLASTIC AGENT; CARRIER PROTEIN; CASP3 PROTEIN, MOUSE; EIF4EBP1 PROTEIN, MOUSE; ERBB2 PROTEIN, HUMAN; KI 67 ANTIGEN; MECHANISTIC TARGET OF RAPAMYCIN COMPLEX 1; MORPHOLINE DERIVATIVE; MULTIPROTEIN COMPLEX; NVP-BKM120; PHOSPHOPROTEIN; TARGET OF RAPAMYCIN KINASE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BIOLUMINESCENCE; BLOOD BRAIN BARRIER; BRAIN METASTASIS; BREAST CANCER; BREAST METASTASIS; CANCER PATIENT; CANCER REGRESSION; CANCER SURVIVAL; COMPARATIVE STUDY; CONTROLLED STUDY; COPY NUMBER VARIATION; DNA REPAIR; DRUG EFFICACY; DRUG POTENTIATION; ENZYME ACTIVITY; ENZYME INHIBITION; FEMALE; GENE MUTATION; GENOMIC INSTABILITY; HUMAN; MOUSE; MUTATION RATE; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; SYSTEMIC THERAPY; TREATMENT RESPONSE; TUMOR MICROENVIRONMENT; TUMOR REGRESSION; TUMOR XENOGRAFT; ANIMAL; ANTAGONISTS AND INHIBITORS; APOPTOSIS; BRAIN NEOPLASMS; BREAST NEOPLASMS; CANCER TRANSPLANTATION; COMBINATION DRUG THERAPY; DRUG EFFECTS; DRUG RESISTANCE; DRUG SCREENING; GENE EXPRESSION PROFILING; GENETICS; IMMUNOHISTOCHEMISTRY; METABOLISM; MOLECULARLY TARGETED THERAPY; PATHOLOGY; PHOSPHORYLATION; REMISSION; SCID MOUSE; SECONDARY;

AMINOPYRIDINES; ANIMALS; ANTINEOPLASTIC AGENTS; APOPTOSIS; BRAIN NEOPLASMS; BREAST NEOPLASMS; CARRIER PROTEINS; CASPASE 3; DNA REPAIR; DRUG RESISTANCE, NEOPLASM; DRUG THERAPY, COMBINATION; EVEROLIMUS; FEMALE; GENE EXPRESSION PROFILING; GENOMIC INSTABILITY; HUMANS; IMMUNOHISTOCHEMISTRY; KI-67 ANTIGEN; MAGNETIC RESONANCE IMAGING; MICE; MICE, SCID; MOLECULAR TARGETED THERAPY; MORPHOLINES; MULTIPROTEIN COMPLEXES; NEOPLASM TRANSPLANTATION; PHOSPHATIDYLINOSITOL 3-KINASES; PHOSPHOPROTEINS; PHOSPHORYLATION; RECEPTOR, ERBB-2; REMISSION INDUCTION; TOR SERINE-THREONINE KINASES; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84976333465     PISSN: 10788956     EISSN: 1546170X     Source Type: Journal    
DOI: 10.1038/nm.4120     Document Type: Article

References (17)

1. Wikman, H. et al. Breast Cancer Res. 14, R49 (2012).
2. Zhang, L. et al. Nature 527, 100-104 (2015).
3. Filbin, M.G. et al. Nat. Med. 19, 1518-1523 (2013).
4. Maire, C.L. et al. Stem Cells 32, 313-326 (2014).
5. Thorpe, L.M., Yuzugullu, H. & Zhao, J.J. Nat. Rev. Cancer 15, 7-24 (2015).
6. Elkabets, M. et al. Sci. Transl. Med. 5, 196ra199 (2013).
7. Krueger, D.A. et al. N. Engl. J. Med. 363, 1801-1811 (2010).
8. O'Reilly, T. et al. Cancer Chemother. Pharmacol. 65, 625-639 (2010).
9. Choo, A.Y., Yoon, S.O., Kim, S.G., Roux, P.P. & Blenis, J. Proc. Natl. Acad. Sci. USA 105, 17414-17419 (2008).
10. Creighton, C.J. Oncogene 26, 4648-4655 (2007).
11. Brastianos, P.K. et al. Cancer Discov. 5, 1164-1177 (2015).
12. Shlien, A. et al. Biallelic Mismatch Repair Deficiency Consortium. Nat. Genet. 47, 257-262 (2015).
13. Hortobagyi, G.N. et al. J. Clin. Oncol. 34, 419-426 (2016).
14. Gentleman, R.C. et al. Genome Biol. 5, R80 (2004).
15. Miller, C.A., Hampton, O., Coarfa, C. & Milosavljevic, A. PLoS One 6, e16327 (2011).
16. Wang, Y. et al. Cell 163, 174-186 (2015).
17. Love, M.I., Huber, W. & Anders, S. Genome Biol. 15, 550 (2014).