Anticipating mechanisms of resistance to PI3K inhibition in breast cancer: A challenge in the era of precision medicine

Biochemical Society Transactions

Volumn 42, Issue 4, 2014, Pages 733-741

  Leroy, Cedric ^a   Amante, Romain J ^a   Bentires Alj, Mohamed ^a  

^a FRIEDRICH MIESCHER INSTITUTE FOR BIOMEDICAL RESEARCH   (Switzerland)

Author keywords

Breast cancer; Drug resistance; Phosphoinositide 3 kinase (PI3K); Signalling; Targeted therapy

Indexed keywords

ANTINEOPLASTIC AGENT; INITIATION FACTOR 4E; MAMMALIAN TARGET OF RAPAMYCIN INHIBITOR; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3 KINASE ALPHA INHIBITOR; PHOSPHATIDYLINOSITOL 3 KINASE BETA INHIBITOR; PHOSPHATIDYLINOSITOL 3 KINASE INHIBITOR; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PROTEIN KINASE B INHIBITOR; PROTEIN TYROSINE KINASE; UNCLASSIFIED DRUG; PIK3CA PROTEIN, HUMAN;

BREAST CANCER; CANCER CELL; CANCER COMBINATION CHEMOTHERAPY; CANCER RECURRENCE; CANCER RESISTANCE; CONFERENCE PAPER; ENZYME ACTIVATION; ENZYME INHIBITION; EPIGENETICS; GENE; GENE MUTATION; HUMAN; INITIATION FACTOR 4E GENE; MOLECULARLY TARGETED THERAPY; NONHUMAN; ONCOGENE MYC; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PIK3CA GENE; PRIORITY JOURNAL; PROTEIN DEPLETION; PROTEIN TARGETING; SIGNAL TRANSDUCTION; ANTAGONISTS AND INHIBITORS; BREAST NEOPLASMS; DRUG RESISTANCE; ENZYMOLOGY; FEMALE; METABOLISM;

ANTINEOPLASTIC AGENTS; BREAST NEOPLASMS; DRUG RESISTANCE, NEOPLASM; FEMALE; HUMANS; PHOSPHATIDYLINOSITOL 3-KINASES;

EID: 84905859015     PISSN: 03005127     EISSN: 14708752     Source Type: Journal    
DOI: 10.1042/BST20140034     Document Type: Conference Paper

References (60)

1. Yuan, T.L. and Cantley, L.C. (2008) PI3K pathway alterations in cancer: variations on a theme. Oncogene 27, 5497-5510
2. Kumar, A. and Carrera, A.C. (2007) New functions for PI3K in the control of cell division. Cell Cycle 6, 1696-1698
3. Chang, H.W., Aoki, M., Fruman, D., Auger, K.R., Bellacosa, A., Tsichlis, P.N., Cantley, L.C., Roberts, T.M. and Vogt, P.K. (1997) Transformation of chicken cells by the gene encoding the catalytic subunit of PI 3-kinase. Science 276, 1848-1850
4. Bader, A.G., Kang, S. and Vogt, P.K. (2006) Cancer-specific mutations in PIK3CA are oncogenic in vivo. Proc. Natl. Acad. Sci. U.S.A. 103, 1475-1479
5. Saxena, R., Chandra, V., Manohar, M., Hajela, K., Debnath, U., Prabhakar, Y.S., Saini, K.S., Konwar, R., Kumar, S., Megu, K. et al. (2013) Chemotherapeutic potential of 2-[piperidinoethoxyphenyl]-3-phenyl-2H-benzo(b) pyran in estrogen receptor-negative breast cancer cells: action via prevention of EGFR activation and combined inhibition of PI-3-K/Akt/FOXO and MEK/Erk/AP-1 pathways. PLoS ONE 8, e66246
6. Chen, Y., Wei, H., Liu, F. and Guan, J.L. (2014) Hyper-activation of mTORC1 promotes breast cancer progression through enhancing glucose starvation-induced autophagy and Akt signaling. J. Biol. Chem. 289, 1164-1173
7. Saal, L.H., Holm, K., Maurer, M., Memeo, L., Su, T., Wang, X., Yu, J.S., Malmstrom, P.O., Mansukhani, M., Enoksson, J. et al. (2005) PIK3CA mutations correlate with hormone receptors, node metastasis, and ERBB2, and are mutually exclusive with PTEN loss in human breast carcinoma. Cancer Res. 65, 2554-2559
8. Stemke-Hale, K., Gonzalez-Angulo, A.M., Lluch, A., Neve, R.M., Kuo, W.L., Davies, M., Carey, M., Hu, Z., Guan, Y., Sahin, A. et al. (2008) An integrative genomic and proteomic analysis of PIK3CA, PTEN, and AKT mutations in breast cancer. Cancer Res. 68, 6084-6091
9. Meyer, D.S., Brinkhaus, H., Müller, U., Müller, M., Cardiff, R.D. and Bentires-Alj, M. (2011) Luminal expression of PIK3CA mutant H1047R in the mammary gland induces heterogeneous tumors. Cancer Res. 71, 4344-4351
10. Koren, S. and Bentires-Alj, M. (2013) Mouse models of PIK3CA mutations: one mutation initiates heterogeneous mammary tumors. FEBS J. 280, 2758-2765
11. Meyer, D.S., Aceto, N., Sausgruber, N., Brinkhaus, H., Müller, U., Pallen, C.J. and Bentires-Alj, M. (2014) Tyrosine phosphatase PTP? contributes to HER2-evoked breast tumor initiation and maintenance. Oncogene 16, 398-402
12. O'Brien, C., Wallin, J.J., Sampath, D., GuhaThakurta, D., Savage, H., Punnoose, E.A., Guan, J., Berry, L., Prior, W.W., Amler, L.C. et al. (2010) Predictive biomarkers of sensitivity to the phosphatidylinositol 3 kinase inhibitor GDC-0941 in breast cancer preclinical models. Clin. Cancer Res. 16, 3670-3683
13. Rhei, E., Kang, L., Bogomolniy, F., Federici, M.G., Borgen, P.I. and Boyd, J. (1997) Mutation analysis of the putative tumor suppressor gene PTEN/MMAC1 in primary breast carcinomas. Cancer Res. 57, 3657-3659
14. Gonzalez-Angulo, A.M., Ferrer-Lozano, J., Stemke-Hale, K., Sahin, A., Liu, S., Barrera, J.A., Burgues, O., Lluch, A.M., Chen, H., Hortobagyi, G.N. et al. (2011) PI3K pathway mutations and PTEN levels in primary and metastatic breast cancer. Mol. Cancer Ther. 10, 1093-1101
15. Poliseno, L., Salmena, L., Zhang, J., Carver, B., Haveman, W.J. and Pandolfi, P.P. (2010) A coding-independent function of gene and pseudogene mRNAs regulates tumour biology. Nature 465, 1033-1038
16. Kim, H., Huang, W., Jiang, X., Pennicooke, B., Park, P.J. and Johnson, M.D. (2010) Integrative genome analysis reveals an oncomir/oncogene cluster regulating glioblastoma survivorship. Proc. Natl. Acad. Sci. U.S.A. 107, 2183-2188
17. Wiencke, J.K., Zheng, S., Jelluma, N., Tihan, T., Vandenberg, S., Tamguney, T., Baumber, R., Parsons, R., Lamborn, K.R., Berger, M.S. et al. (2007) Methylation of the PTEN promoter defines low-grade gliomas and secondary glioblastoma. Neuro Oncol. 9, 271-279
18. Jones, N., Bonnet, F., Sfar, S., Lafitte, M., Lafon, D., Sierankowski, G., Brouste, V., Banneau, G., Tunon de Lara, C., Debled, M. et al. (2013) Comprehensive analysis of PTEN status in breast carcinomas. Int. J. Cancer 133, 323-334
19. Rodon, J., Dienstmann, R., Serra, V. and Tabernero, J. (2013) Development of PI3K inhibitors: lessons learned from early clinical trials. Nat. Rev. Clin. Oncol. 10, 143-153
20. Maira, S.M., Stauffer, F., Brueggen, J., Furet, P., Schnell, C., Fritsch, C., Brachmann, S., Chene, P., De Pover, A., Schoemaker, K. et al. (2008) Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity. Mol. Cancer Ther. 7, 1851-1863
21. Folkes, A.J., Ahmadi, K., Alderton, W.K., Alix, S., Baker, S.J., Box, G., Chuckowree, I.S., Clarke, P.A., Depledge, P., Eccles, S.A. et al. (2008) The identification of 2-(1H-indazol-4-yl)-6-(4-methanesulfonyl-piperazin-1- ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine (GDC-0941) as a potent, selective, orally bioavailable inhibitor of class I PI3 kinase for the treatment of cancer. J. Med. Chem. 51, 5522-5532
22. Markman, B., Atzori, F., Perez-Garcia, J., Tabernero, J. and Baselga, J. (2010) Status of PI3K inhibition and biomarker development in cancer therapeutics. Ann. Oncol. 21, 683-691
23. Maira, S.M., Pecchi, S., Huang, A., Burger, M., Knapp, M., Sterker, D., Schnell, C., Guthy, D., Nagel, T., Wiesmann, M. et al. (2012) Identification and characterization of NVP-BKM120, an orally available pan-class I PI3-kinase inhibitor. Mol. Cancer Ther. 11, 317-328
24. Nanni, P., Nicoletti, G., Palladini, A., Croci, S., Murgo, A., Ianzano, M.L., Grosso, V., Stivani, V., Antognoli, A., Lamolinara, A. et al. (2012) Multiorgan metastasis of human HER-2+ breast cancer in Rag2/ ;Il2rg/ mice and treatment with PI3K inhibitor. PLoS ONE 7, e39626
25. So, L., Yea, S.S., Oak, J.S., Lu, M., Manmadhan, A., Ke, Q.H., Janes, M.R., Kessler, L.V., Kucharski, J.M., Li, L.S. et al. (2013) Selective inhibition of phosphoinositide 3-kinase p110 preserves lymphocyte function. J. Biol. Chem. 288, 5718-5731
26. Martini, M., Ciraolo, E., Gulluni, F. and Hirsch, E. (2013) Targeting PI3K in cancer: any good news? Front. Oncol. 3, 108
27. Huang, A., Fritsch, C., Wilson, C., Reddy, A., Liu, M., Lehar, J., Quadt, C., Hofmann, F. and Schlegel, R. (2012), Single agent activity of PIK3CA inhibitor BYL719 in a broad cancer cell line panel. AACR Annual Meeting 2012, Chicago, IL, U.S.A., 31 March-4 April 2012, Abstract 3749
28. Busaidy, N.L., Farooki, A., Dowlati, A., Perentesis, J.P., Dancey, J.E., Doyle, L.A., Brell, J.M. and Siu, L.L. (2012) Management of metabolic effects associated with anticancer agents targeting the PI3K-Akt-mTOR pathway. J. Clin. Oncol. 30, 2919-2928
29. Jia, S., Liu, Z., Zhang, S., Liu, P., Zhang, L., Lee, S.H., Zhang, J., Signoretti, S., Loda, M., Roberts, T.M. et al. (2008) Essential roles of PI(3)K-p110β in cell growth, metabolism and tumorigenesis. Nature 454, 776-779
30. Wee, S., Wiederschain, D., Maira, S.M., Loo, A., Miller, C., deBeaumont, R., Stegmeier, F., Yao, Y.M. and Lengauer, C. (2008) PTEN-deficient cancers depend on PIK3CB. Proc. Natl. Acad. Sci. U.S.A. 105, 13057-13062
31. Ni, J., Liu, Q., Xie, S., Carlson, C., Von, T., Vogel, K., Riddle, S., Benes, C., Eck, M., Roberts, T. et al. (2012) Functional characterization of an isoform-selective inhibitor of PI3K-p110β as a potential anticancer agent. Cancer Discov. 2, 425-433
32. Certal, V., Halley, F., Virone-Oddos, A., Delorme, C., Karlsson, A., Rak, A., Thompson, F., Filoche-Romme, B., El-Ahmad, Y., Carry, J.C. et al. (2012) Discovery and optimization of new benzimidazole- and benzoxazole-pyrimidone selective PI3Kβ inhibitors for the treatment of phosphatase and TENsin homologue (PTEN)-deficient cancers. J. Med. Chem. 55, 4788-4805
33. Radimerski, T., Montagne, J., Hemmings-Mieszczak, M. and Thomas, G. (2002) Lethality of Drosophila lacking TSC tumor suppressor function rescued by reducing dS6K signaling. Genes Dev. 16, 2627-2632
34. Harrington, L.S., Findlay, G.M., Gray, A., Tolkacheva, T., Wigfield, S., Rebholz, H., Barnett, J., Leslie, N.R., Cheng, S., Shepherd, P.R. et al. (2004) The TSC1-2 tumor suppressor controls insulin-PI3K signaling via regulation of IRS proteins. J. Cell Biol. 166, 213-223
35. Haruta, T., Uno, T., Kawahara, J., Takano, A., Egawa, K., Sharma, P.M., Olefsky, J.M. and Kobayashi, M. (2000) A rapamycin-sensitive pathway down-regulates insulin signaling via phosphorylation and proteasomal degradation of insulin receptor substrate-1. Mol. Endocrinol. 14, 783-794
36. Chan, S., Scheulen, M.E., Johnston, S., Mross, K., Cardoso, F., Dittrich, C., Eiermann, W., Hess, D., Morant, R., Semiglazov, V. et al. (2005) Phase II study of temsirolimus (CCI-779), a novel inhibitor of mTOR, in heavily pretreated patients with locally advanced or metastatic breast cancer. J. Clin. Oncol. 23, 5314-5322
37. Wolff, A.C., Lazar, A.A., Bondarenko, I., Garin, A.M., Brincat, S., Chow, L., Sun, Y., Neskovic-Konstantinovic, Z., Guimaraes, R.C., Fumoleau, P. et al. (2013) Randomized phase III placebo-controlled trial of letrozole plus oral temsirolimus as first-line endocrine therapy in postmenopausal women with locally advanced or metastatic breast cancer. J. Clin. Oncol. 31, 195-202
38. O'Reilly, K.E., Rojo, F., She, Q.B., Solit, D., Mills, G.B., Smith, D., Lane, H., Hofmann, F., Hicklin, D.J., Ludwig, D.L. et al. (2006) mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt. Cancer Res. 66, 1500-1508
39. Choo, A.Y., Yoon, S.O., Kim, S.G., Roux, P.P. and Blenis, J. (2008) Rapamycin differentially inhibits S6Ks and 4E-BP1 to mediate cell-type-specific repression of mRNA translation. Proc. Natl. Acad. Sci. U.S.A. 105, 17414-17419
40. Klempner, S.J., Myers, A.P. and Cantley, L.C. (2013) What a tangled web we weave: emerging resistance mechanisms to inhibition of the phosphoinositide 3-kinase pathway. Cancer Discov. 3, 1345-1354
41. Carracedo, A., Ma, L., Teruya-Feldstein, J., Rojo, F., Salmena, L., Alimonti, A., Egia, A., Sasaki, A.T., Thomas, G., Kozma, S.C. et al. (2008) Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer. J. Clin. Invest. 118, 3065-3074
42. Muranen, T., Selfors, L.M., Worster, D.T., Iwanicki, M.P., Song, L., Morales, F.C., Gao, S., Mills, G.B. and Brugge, J.S. (2012) Inhibition of PI3K/mTOR leads to adaptive resistance in matrix-attached cancer cells. Cancer Cell 21, 227-239
43. Britschgi, A., Andraos, R., Brinkhaus, H., Klebba, I., Romanet, V., Müller, U., Murakami, M., Radimerski, T. and Bentires-Alj, M. (2012) JAK2/STAT5 inhibition circumvents resistance to PI3K/mTOR blockade: a rationale for cotargeting these pathways in metastatic breast cancer. Cancer Cell 22, 796-811
44. Britschgi, A., Radimerski, T. and Bentires-Alj, M. (2013) Targeting PI3K, HER2 and the IL-8/JAK2 axis in metastatic breast cancer: which combination makes the whole greater than the sum of its parts? Drug Resist. Updat. 16, 68-72
45. Serra, V., Scaltriti, M., Prudkin, L., Eichhorn, P.J., Ibrahim, Y.H., Chandarlapaty, S., Markman, B., Rodriguez, O., Guzman, M., Rodriguez, S. et al. (2011) PI3K inhibition results in enhanced HER signaling and acquired ERK dependency in HER2-overexpressing breast cancer. Oncogene 30, 2547-2557
46. Chandarlapaty, S., Sawai, A., Scaltriti, M., Rodrik-Outmezguine, V., Grbovic-Huezo, O., Serra, V., Majumder, P.K., Baselga, J. and Rosen, N. (2011) AKT inhibition relieves feedback suppression of receptor tyrosine kinase expression and activity. Cancer Cell 19, 58-71
47. Ilic, N., Utermark, T., Widlund, H.R. and Roberts, T.M. (2011) PI3K-targeted therapy can be evaded by gene amplification along the MYC-eukaryotic translation initiation factor 4E (eIF4E) axis. Proc. Natl. Acad. Sci. U.S.A. 108, E699-E708
48. Muellner, M.K., Uras, I.Z., Gapp, B.V., Kerzendorfer, C., Smida, M., Lechtermann, H., Craig-Mueller, N., Colinge, J., Duernberger, G. and Nijman, S.M. (2011) A chemical-genetic screen reveals a mechanism of resistance to PI3K inhibitors in cancer. Nat. Chem. Biol. 7, 787-793
49. Brachmann, S.M., Hofmann, I., Schnell, C., Fritsch, C., Wee, S., Lane, H., Wang, S., Garcia-Echeverria, C. and Maira, S.M. (2009) Specific apoptosis induction by the dual PI3K/mTor inhibitor NVP-BEZ235 in HER2 amplified and PIK3CA mutant breast cancer cells. Proc. Natl. Acad. Sci. U.S.A. 106, 22299-22304
50. Serra, V., Eichhorn, P.J., Garcia-Garcia, C., Ibrahim, Y.H., Prudkin, L., Sanchez, G., Rodriguez, O., Anton, P., Parra, J.L., Marlow, S. et al. (2013) RSK3/4 mediate resistance to PI3K pathway inhibitors in breast cancer. J. Clin. Invest. 123, 2551-2563
51. Elkabets, M., Vora, S., Juric, D., Morse, N., Mino-Kenudson, M., Muranen, T., Tao, J., Campos, A.B., Rodon, J., Ibrahim, Y.H. et al. (2013) mTORC1 inhibition is required for sensitivity to PI3K p110 inhibitors in PIK3CA-mutant breast cancer. Sci. Transl. Med. 5, 196ra199
52. Fox, E.M., Arteaga, C.L. and Miller, T.W. (2012) Abrogating endocrine resistance by targeting ER and PI3K in breast cancer. Front. Oncol. 2, 145
53. Miller, T.W., Hennessy, B.T., Gonzalez-Angulo, A.M., Fox, E.M., Mills, G.B., Chen, H., Higham, C., Garcia-Echeverria, C., Shyr, Y. and Arteaga, C.L. (2010) Hyperactivation of phosphatidylinositol-3 kinase promotes escape from hormone dependence in estrogen receptor-positive human breast cancer. J. Clin. Invest. 120, 2406-2413
54. Dhillon, S. (2013) Everolimus in combination with exemestane: a review of its use in the treatment of patients with postmenopausal hormone receptor-positive, HER2-negative advanced breast cancer. Drugs 73, 475-485
55. Chakrabarty, A., Bhola, N.E., Sutton, C., Ghosh, R., Kuba, M.G., Dave, B., Chang, J.C. and Arteaga, C.L. (2013) Trastuzumab-resistant cells rely on a HER2-PI3K-FoxO-survivin axis and are sensitive to PI3K inhibitors. Cancer Res. 73, 1190-1200
56. Yao, E., Zhou, W., Lee-Hoeflich, S.T., Truong, T., Haverty, P.M., Eastham-Anderson, J., Lewin-Koh, N., Gunter, B., Belvin, M., Murray, L.J. et al. (2009) Suppression of HER2/HER3-mediated growth of breast cancer cells with combinations of GDC-0941 PI3K inhibitor, trastuzumab, and pertuzumab. Clin. Cancer Res. 15, 4147-4156
57. Brady, S.W., Zhang, J., Seok, D., Wang, H. and Yu, D. (2014) Enhanced PI3K p110 signaling confers acquired lapatinib resistance which can be effectively reversed by a p110-selective PI3K inhibitor. Mol. Cancer Ther. 13, 60-70
58. Ibrahim, Y.H., Garcia-Garcia, C., Serra, V., He, L., Torres-Lockhart, K., Prat, A., Anton, P., Cozar, P., Guzman, M., Grueso, J. et al. (2012) PI3K inhibition impairs BRCA1/2 expression and sensitizes BRCA-proficient triple-negative breast cancer to PARP inhibition. Cancer Discov. 2, 1036-1047
59. Juvekar, A., Burga, L.N., Hu, H., Lunsford, E.P., Ibrahim, Y.H., Balmana, J., Rajendran, A., Papa, A., Spencer, K., Lyssiotis, C.A. et al. (2012) Combining a PI3K inhibitor with a PARP inhibitor provides an effective therapy for BRCA1-related breast cancer. Cancer Discov. 2, 1048-1063
60. Saini, K.S., Loi, S., de Azambuja, E., Metzger-Filho, O., Saini, M.L., Ignatiadis, M., Dancey, J.E. and Piccart-Gebhart, M.J. (2013) Targeting the PI3K/AKT/mTOR and Raf/MEK/ERK pathways in the treatment of breast cancer. Cancer Treat. Rev. 39, 935-946