AKT antagonist AZD5363 influences estrogen receptor function in endocrine-resistant breast cancer and synergizes with fulvestrant (ICI182780) in vivo

Molecular Cancer Therapeutics

Volumn 14, Issue 9, 2015, Pages 2035-2048

  Ribas, Ricardo ^a   Pancholi, Sunil ^a   Guest, Stephanie K ^a   Marangoni, Elisabetta ^b   Gao, Qiong ^a   Thuleau, Aurélie ^b   Simigdala, Nikiana ^a   Polanska, Urszula M ^c   Campbell, Hayley ^c   Rani, Aradhana ^a   Liccardi, Gianmaria ^a   Johnston, Stephen ^d   Davies, Barry R ^c   Dowsett, Mitch ^a,d   Martin, Lesley Ann ^a  

^a INSTITUTE OF CANCER RESEARCH   (United Kingdom)

^b INSTITUT CURIE   (France)

^c ASTRAZENECA   (United Kingdom)

^d ROYAL MARSDEN HOSPITAL   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

4 AMINO N [1 (4 CHLOROPHENYL) 3 HYDROXYPROPYL] 1 (7H PYRROLO[2,3 D]PYRIMIDIN 4 YL) 4 PIPERIDINECARBOXAMIDE; AFIMOXIFENE; ESTROGEN RECEPTOR; FULVESTRANT; LETROZOLE; MAMMALIAN TARGET OF RAPAMYCIN; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; PROTEIN TYROSINE KINASE; 4-AMINO-N-(1-(4-CHLOROPHENYL)-3-HYDROXYPROPYL)-1-(7H-PYRROLO(2,3-D)PYRIMIDIN-4-YL)PIPERIDINE-4-CARBOXAMIDE; ANTINEOPLASTIC HORMONE AGONISTS AND ANTAGONISTS; ESTRADIOL; MYC PROTEIN; PROTEIN KINASE INHIBITOR; PYRIMIDINE DERIVATIVE; PYRROLE DERIVATIVE; TARGET OF RAPAMYCIN KINASE;

ANIMAL MODEL; ANTIPROLIFERATIVE ACTIVITY; ARTICLE; BREAST CANCER; BREAST CANCER CELL LINE; CANCER GROWTH; CANCER HORMONE THERAPY; CANCER INHIBITION; CANCER RESISTANCE; CANCER SIZE; CELL PROLIFERATION; CLINICAL EVALUATION; COMPARATIVE STUDY; CONTROLLED STUDY; DRUG EFFECT; DRUG EFFICACY; DRUG POTENTIATION; DRUG RESPONSE; ENZYME ACTIVITY; ENZYME PHOSPHORYLATION; FEEDING; FEMALE; GENE EXPRESSION; HUMAN; HUMAN CELL; HUMAN TISSUE; IN VIVO STUDY; MCF 7 CELL LINE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN FUNCTION; SIGNAL TRANSDUCTION; TRANSACTIVATION; TUMOR GROWTH INHIBITION (PERCENTAGE); ANALOGS AND DERIVATIVES; ANIMAL; ANTAGONISTS AND INHIBITORS; BREAST NEOPLASMS; CELL CYCLE CHECKPOINT; CLUSTER ANALYSIS; DISEASE MODEL; DRUG EFFECTS; DRUG RESISTANCE; DRUG SCREENING; GENE EXPRESSION PROFILING; GENETICS; METABOLISM; PATHOLOGY; TRANSCRIPTION INITIATION; TUMOR CELL LINE;

ANIMALS; ANTINEOPLASTIC AGENTS, HORMONAL; BREAST NEOPLASMS; CELL CYCLE CHECKPOINTS; CELL LINE, TUMOR; CELL PROLIFERATION; CLUSTER ANALYSIS; DISEASE MODELS, ANIMAL; DRUG RESISTANCE, NEOPLASM; DRUG SYNERGISM; ESTRADIOL; FEMALE; GENE EXPRESSION PROFILING; HUMANS; MICE; PHOSPHATIDYLINOSITOL 3-KINASES; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS C-AKT; PROTO-ONCOGENE PROTEINS C-MYC; PYRIMIDINES; PYRROLES; RECEPTORS, ESTROGEN; SIGNAL TRANSDUCTION; TOR SERINE-THREONINE KINASES; TRANSCRIPTIONAL ACTIVATION; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84942163532     PISSN: 15357163     EISSN: 15388514     Source Type: Journal    
DOI: 10.1158/1535-7163.MCT-15-0143     Document Type: Article

References (43)

1. Dowsett M, Howell A. Breast cancer: aromatase inhibitors take on tamoxifen. Nat Med 2002;8:1341-4.
2. Shaw RJ, Cantley LC. Ras, PI(3)K and mTOR signalling controls tumour cell growth. Nature 2006;441:424-30.
3. Shoman N, Klassen S, McFadden A, Bickis MG, Torlakovic E, Chibbar R. Reduced PTEN expression predicts relapse in patients with breast carcinoma treated by tamoxifen. Mod Pathol 2005;18:250-9.
4. Clark AS, West K, Streicher S, Dennis PA. Constitutive and inducible Akt activity promotes resistance to chemotherapy, trastuzumab, or tamoxifen in breast cancer cells. Mol Cancer Ther 2002;1:707-17.
5. Yu K, Toral-Barza L, Discafani C, Zhang WG, Skotnicki J, Frost P, et al. mTOR, a novel target in breast cancer: the effect of CCI-779, an mTOR inhibitor, in preclinical models of breast cancer. Endocr Relat Cancer 2001;8:249-58.
6. Saal LH, Holm K, Maurer M, Memeo L, Su T, Wang X, et al. PIK3CA mutations correlate with hormone receptors, node metastasis, and ERBB2, and are mutually exclusive with PTEN loss in human breast carcinoma. Cancer Res 2005;65:2554-9.
7. Simoncini T, Hafezi-Moghadam A, Brazil DP, Ley K, Chin WW, Liao JK. Interaction of oestrogen receptor with the regulatory subunit of phosphatidylinositol-3-OH kinase. Nature 2000;407:538-41.
8. Miller TW, Hennessy BT, Gonzalez-Angulo AM, Fox EM, Mills GB, Chen H, et al. Hyperactivation of phosphatidylinositol-3 kinase promotes escape from hormone dependence in estrogen receptor-positive human breast cancer. J Clin Invest 2010;120:2406-13.
9. Chen D, Washbrook E, Sarwar N, Bates GJ, Pace PE, Thirunuvakkarasu V, et al. Phosphorylation of human estrogen receptor alpha at serine 118 by two distinct signal transduction pathways revealed by phosphorylation-specific antisera. Oncogene 2002;21:4921-31.
10. Campbell RA, Bhat-Nakshatri P, Patel NM, Constantinidou D, Ali S, Nakshatri H. Phosphatidylinositol 3-kinase/AKT-mediated activation of estrogen receptor alpha: a new model for anti-estrogen resistance. J Biol Chem 2001;276:9817-24.
11. Kato S, Endoh H, Masuhiro Y, Kitamoto T, Uchiyama S, Sasaki H, et al. Activation of the estrogen receptor through phosphorylation by mitogen-activated protein kinase. Science 1995;270:1491-4.
12. Smith CL. Cross-talk between peptide growth factor and estrogen receptor signaling pathways. Biol Reprod 1998;58:627-32.
13. Bhat-Nakshatri P, Wang G, Appaiah H, Luktuke N, Carroll JS, Geistlinger TR, et al. AKT alters genome-wide estrogen receptor alpha binding and impacts estrogen signaling in breast cancer. Mol Cell Biol 2008;28:7487-503.
14. O'Reilly KE, Rojo F, She QB, Solit D, Mills GB, Smith D, et al. mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt. Cancer Res 2006;66:1500-8.
15. Sun SY, Rosenberg LM, Wang X, Zhou Z, Yue P, Fu H, et al. Activation of Akt and eIF4E survival pathways by rapamycin-mediated mammalian target of rapamycin inhibition. Cancer Res 2005;65:7052-8.
16. Davies BR, Greenwood H, Dudley P, Crafter C, Yu DH, Zhang J, et al. Preclinical pharmacology of AZD5363, an inhibitor of AKT: pharmacodynamics, antitumor activity, and correlation of monotherapy activity with genetic background. Mol Cancer Ther 2012;11:873-87.
17. Fox EM, Kuba MG, Miller TW, Davies BR, Arteaga CL. Autocrine IGF-I/insulin receptor axis compensates for inhibition of AKT in ER-positive breast cancer cells with resistance to estrogen deprivation. Breast Cancer Res 2013;15:R55.
18. Martin LA, Farmer I, Johnston SR, Ali S, Marshall C, Dowsett M. Enhanced estrogen receptor (ER) alpha, ERBB2, and MAPK signal transduction pathways operate during the adaptation of MCF-7 cells to long term estrogen deprivation. J Biol Chem 2003;278:30458-68.
19. Pancholi S, Lykkesfeldt AE, Hilmi C, Banerjee S, Leary A, Drury S, et al. ERBB2 influences the subcellular localization of the estrogen receptor in tamoxifen-resistant MCF-7 cells leading to the activation of AKT and RPS6KA2. Endocr Relat Cancer 2008;15:985-1002.
20. Banerjee S, Zvelebil M, Furet P, Mueller-Vieira U, Evans DB, Dowsett M, et al. The vascular endothelial growth factor receptor inhibitor PTK787/ZK222584 inhibits aromatase. Cancer Res 2009;69:4716-23.
21. Chou TC, Talalay P. Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul 1984;22:27-55.
22. Cottu P, Bieche I, Assayag F, El Botty R, Chateau-Joubert S, Thuleau A, et al. Acquired resistance to endocrine treatments is associated with tumor-specific molecular changes in patient-derived luminal breast cancer xenografts. Clin Cancer Res 2014;20:4314-25.
23. Ali S, Coombes RC. Endocrine-responsive breast cancer and strategies for combating resistance. Nat Rev Cancer 2002;2:101-12.
24. Stossi F, Likhite VS, Katzenellenbogen JA, Katzenellenbogen BS. Estrogen-occupied estrogen receptor represses cyclin G2 gene expression and recruits a repressor complex at the cyclin G2 promoter. J Biol Chem 2006;281:16272-8.
25. Martinez-Gac L, Alvarez B, Garcia Z, Marques M, Arrizabalaga M, Carrera AC. Phosphoinositide 3-kinase and Forkhead, a switch for cell division. Biochem Soc Trans 2004;32:360-1.
26. Okuzumi T, Fiedler D, Zhang C, Gray DC, Aizenstein B, Hoffman R, et al. Inhibitor hijacking of Akt activation. Nat Chem Biol 2009;5:484-93.
27. Zha J, Harada H, Yang E, Jockel J, Korsmeyer SJ. Serine phosphorylation of death agonist BAD in response to survival factor results in binding to 14-3-3 not BCL-X(L). Cell 1996;87:619-28.
28. Bosch A, Li Z, Bergamaschi A, Ellis H, Toska E, Prat A, et al. PI3K inhibition results in enhanced estrogen receptor function and dependence in hormone receptor-positive breast cancer. Sci Transl Med 2015;7:283ra51.
29. Chakrabarty A, Sanchez V, Kuba MG, Rinehart C, Arteaga CL. Feedback upregulation of HER3 (ErbB3) expression and activity attenuates antitumor effect of PI3K inhibitors. Proc Natl Acad Sci U S A 2012;109:2718-23.
30. Chandarlapaty S, Sawai A, Scaltriti M, Rodrik-Outmezguine V, Grbovic-Huezo O, Serra V, et al. AKT inhibition relieves feedback suppression of receptor tyrosine kinase expression and activity. Cancer Cell 2011;19:58-71.
31. Rodrik-Outmezguine VS, Chandarlapaty S, Pagano NC, Poulikakos PI, Scaltriti M, Moskatel E, et al. mTOR kinase inhibition causes feedback-dependent biphasic regulation of AKT signaling. Cancer Discov 2011;1:248-59.
32. Mounir Z, Krishnamoorthy JL, Wang S, Papadopoulou B, Campbell S, Muller WJ, et al. Akt determines cell fate through inhibition of the PERK-eIF2alpha phosphorylation pathway. Sci Signal 2011;4:ra62.
33. Srinivas H, Xia D, Moore NL, Uray IP, Kim H, Ma L, et al. Akt phosphorylates and suppresses the transactivation of retinoic acid receptor alpha. Biochem J 2006;395:653-62.
34. Ross-Innes CS, Stark R, Holmes KA, Schmidt D, Spyrou C, Russell R, et al. Cooperative interaction between retinoic acid receptor-alpha and estrogen receptor in breast cancer. Genes Dev 2010;24:171-82.
35. Creighton CJ, Fu X, Hennessy BT, Casa AJ, Zhang Y, Gonzalez-Angulo AM, et al. Proteomic and transcriptomic profiling reveals a link between the PI3K pathway and lower estrogen-receptor (ER) levels and activity in ER+ breast cancer. Breast Cancer Res 2010;12:R40.
36. Chen D, Riedl T, Washbrook E, Pace PE, Coombes RC, Egly JM, et al. Activation of estrogen receptor alpha by S118 phosphorylation involves a ligand-dependent interaction with TFIIH and participation of CDK7. Mol Cell 2000;6:127-37.
37. Bour G, Gaillard E, Bruck N, Lalevee S, Plassat JL, Busso D, et al. Cyclin H binding to the RARalpha activation function (AF)-2 domain directs phosphorylation of the AF-1 domain by cyclin-dependent kinase 7. Proc Natl Acad Sci U S A 2005;102:16608-13.
38. Johansson HJ, Sanchez BC, Mundt F, Forshed J, Kovacs A, Panizza E, et al. Retinoic acid receptor alpha is associated with tamoxifen resistance in breast cancer. Nat Commun 2013;4:2175.
39. Nishimoto S, Nishida E. MAPK signalling: ERK5 versus ERK1/2. EMBO Rep 2006;7:782-6.
40. Mongroo PS, Johnstone CN, Naruszewicz I, Leung-Hagesteijn C, Sung RK, Carnio L, et al. Beta-parvin inhibits integrin-linked kinase signaling and is downregulated in breast cancer. Oncogene 2004;23:8959-70.
41. Kimura M, Murakami T, Kizaka-Kondoh S, Itoh M, Yamamoto K, Hojo Y, et al. Functional molecular imaging of ILK-mediated Akt/PKB signaling cascades and the associated role of beta-parvin. J Cell Sci 2010;123:747-55.
42. Morfoisse F, Kuchnio A, Frainay C, Gomez-Brouchet A, Delisle MB, Marzi S, et al. Hypoxia induces VEGF-C expression in metastatic tumor cells via a HIF-1alpha-independent translation-mediated mechanism. Cell Rep 2014;6:155-67.
43. Balakumaran BS, Porrello A, Hsu DS, Glover W, Foye A, Leung JY, et al. MYC activity mitigates response to rapamycin in prostate cancer through eukaryotic initiation factor 4E-binding protein 1-mediated inhibition of autophagy. Cancer Res 2009;69:7803-10.