Rexer BN, Arteaga CL. Intrinsic and acquired resistance to HER2-targeted therapies in HER2 gene-amplified breast cancer: mechanisms and clinical implications. Crit Rev Oncog. 2012;17(1):1–16.
Article
Google Scholar
Luengo A, Gui DY, Vander Heiden MG. Targeting metabolism for cancer therapy. Cell Chem Biol. 2017;24(9):1161–80.
Article
CAS
Google Scholar
Glunde K, Bhujwalla ZM, Ronen SM. Choline metabolism in malignant transformation. Nat Rev Cancer. 2011;11(12):835–48.
Article
CAS
Google Scholar
Iorio E, Caramujo MJ, Cecchetti S, Spadaro F, Carpinelli G, Canese R, et al. Key players in choline metabolic reprograming in triple-negative breast cancer. Front Oncol. 2016;6:205.
Article
Google Scholar
Sonkar K, Ayyappan V, Tressler CM, Adelaja O, Cai R, Cheng M, et al. Focus on the glycerophosphocholine pathway in choline phospholipid metabolism of cancer. NMR Biomed. 2019;32(10):e4112.
Article
Google Scholar
Aboagye EO, Bhujwalla ZM. Malignant transformation alters membrane choline phospholipid metabolism of human mammary epithelial cells. Cancer Res. 1999;59(1):80–4.
CAS
Google Scholar
Chen JH, Mehta RS, Baek HM, Nie K, Liu H, Lin MQ, et al. Clinical characteristics and biomarkers of breast cancer associated with choline concentration measured by 1H MRS. NMR Biomed. 2011;24(3):316–24.
Article
CAS
Google Scholar
Glunde K, Jie C, Bhujwalla ZM. Molecular causes of the aberrant choline phospholipid metabolism in breast cancer. Cancer Res. 2004;64(12):4270–6.
Article
CAS
Google Scholar
Mori N, Wildes F, Takagi T, Glunde K, Bhujwalla ZM. The tumor microenvironment modulates choline and lipid metabolism. Front Oncol. 2016;6:262.
Article
Google Scholar
RamírezdeMolina A, Gutiérrez R, Ramos MA, Silva JM, Silva J, Bonilla F, et al. Increased choline kinase activity in human breast carcinomas: clinical evidence for a potential novel antitumor strategy. Oncogene. 2002;21(27):4317–22.
Article
Google Scholar
Stewart JD, Marchan R, Lesjak MS, Lambert J, Hergenroeder R, Ellis JK, et al. Choline-releasing glycerophosphodiesterase EDI3 drives tumor cell migration and metastasis. Proc Natl Acad Sci U S A. 2012;109(21):8155–60.
Article
CAS
Google Scholar
Lesjak MS, Marchan R, Stewart JD, Rempel E, Rahnenführer J, Hengstler JG. EDI3 links choline metabolism to integrin expression, cell adhesion and spreading. Cell Adh Migr. 2014;8(5):499–508.
Article
Google Scholar
Huang KB, Pan YH, Shu GN, Yao HH, Liu X, Zhou M, et al. Circular RNA circSNX6 promotes sunitinib resistance in renal cell carcinoma through the miR-1184/GPCPD1/ lysophosphatidic acid axis. Cancer Lett. 2021;523:121–34.
Article
CAS
Google Scholar
Marchan R, Büttner B, Lambert J, Edlund K, Glaeser I, Blaszkewicz M, et al. Glycerol-3-phosphate acyltransferase 1 promotes tumor cell migration and poor survival in ovarian carcinoma. Cancer Res. 2017;77(17):4589–601.
Article
CAS
Google Scholar
McCall MN, Bolstad BM, Irizarry RA. Frozen robust multiarray analysis (fRMA). Biostatistics. 2010;11(2):242–53.
Article
Google Scholar
Trost TM, Lausch EU, Fees SA, Schmitt S, Enklaar T, Reutzel D, et al. Premature senescence is a primary fail-safe mechanism of ERBB2-driven tumorigenesis in breast carcinoma cells. Cancer Res. 2005;65(3):840–9.
Article
CAS
Google Scholar
Faustino-Rocha A, Oliveira PA, Pinho-Oliveira J, Teixeira-Guedes C, Soares-Maia R, da Costa RG, et al. Estimation of rat mammary tumor volume using caliper and ultrasonography measurements. Lab Anim (NY). 2013;42(6):217–24.
Article
Google Scholar
Jernström S, Hongisto V, Leivonen SK, Due EU, Tadele DS, Edgren H, et al. Drug-screening and genomic analyses of HER2-positive breast cancer cell lines reveal predictors for treatment response. Breast Cancer (Dove Med Press). 2017;9:185–98.
Google Scholar
Nagata Y, Lan KH, Zhou X, Tan M, Esteva FJ, Sahin AA, et al. PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients. Cancer Cell. 2004;6(2):117–27.
Article
CAS
Google Scholar
Collins DM, Madden SF, Gaynor N, AlSultan D, Le Gal M, Eustace AJ, et al. Effects of HER family-targeting tyrosine kinase inhibitors on antibody-dependent cell-mediated cytotoxicity in HER2-expressing breast cancer. Clin Cancer Res. 2021;27(3):807–18.
Article
CAS
Google Scholar
Hurvitz SA, Kalous O, Conklin D, Desai AJ, Dering J, Anderson L, et al. In vitro activity of the mTOR inhibitor everolimus, in a large panel of breast cancer cell lines and analysis for predictors of response. Breast Cancer Res Treat. 2015;149(3):669–80.
Article
CAS
Google Scholar
Castro-Mondragon JA, Riudavets-Puig R, Rauluseviciute I, Lemma RB, Turchi L, Blanc-Mathieu R, et al. JASPAR 2022: the 9th release of the open-access database of transcription factor binding profiles. Nucleic Acids Res. 2022;50(D1):D165–73.
Article
CAS
Google Scholar
Cartharius K, Frech K, Grote K, Klocke B, Haltmeier M, Klingenhoff A, et al. MatInspector and beyond: promoter analysis based on transcription factor binding sites. Bioinformatics. 2005;21(13):2933–42.
Article
CAS
Google Scholar
Flugel D, Gorlach A, Michiels C, Kietzmann T. Glycogen synthase kinase 3 phosphorylates hypoxia-inducible factor 1alpha and mediates its destabilization in a VHL-independent manner. Mol Cell Biol. 2007;27(9):3253–65.
Article
Google Scholar
Grimes CA, Jope RS. CREB DNA binding activity is inhibited by glycogen synthase kinase-3 beta and facilitated by lithium. J Neurochem. 2001;78(6):1219–32.
Article
CAS
Google Scholar
Bialkowska AB, Liu Y, Nandan MO, Yang VW. A colon cancer-derived mutant of Kruppel-like factor 5 (KLF5) is resistant to degradation by glycogen synthase kinase 3beta (GSK3beta) and the E3 ubiquitin ligase F-box and WD repeat domain-containing 7alpha (FBW7alpha). J Biol Chem. 2014;289(9):5997–6005.
Article
CAS
Google Scholar
Bilsland AE, Hoare S, Stevenson K, Plumb J, Gomez-Roman N, Cairney C, et al. Dynamic telomerase gene suppression via network effects of GSK3 inhibition. PLoS ONE. 2009;4(7):e6459.
Article
Google Scholar
Steven A, Friedrich M, Jank P, Heimer N, Budczies J, Denkert C, et al. What turns CREB on? And off? And why does it matter? Cell Mol Life Sci. 2020;77(20):4049–67.
Article
CAS
Google Scholar
Zhang Y, Zhang H, Wang M, Schmid T, Xin Z, Kozhuharova L, et al. Hypoxia in breast cancer-scientific translation to therapeutic and diagnostic clinical applications. Front Oncol. 2021;11:652266.
Article
Google Scholar
Sonnenblick A, Agbor-Tarh D, de Azambuja E, Hultsch S, Izquierdo M, Liu M, et al. STAT3 activation in HER2-positive breast cancers: Analysis of data from a large prospective trial. Int J Cancer. 2021;148(6):1529–35.
Article
CAS
Google Scholar
Wang W, Nag SA, Zhang R. Targeting the NFkappaB signaling pathways for breast cancer prevention and therapy. Curr Med Chem. 2015;22(2):264–89.
Article
Google Scholar
Hudis CA. Trastuzumab–mechanism of action and use in clinical practice. N Engl J Med. 2007;357(1):39–51.
Article
CAS
Google Scholar
Huang W, Sundquist J, Sundquist K, Ji J. Phosphodiesterase-5 inhibitors use and risk for mortality and metastases among male patients with colorectal cancer. Nat Commun. 2020;11(1):3191.
Article
CAS
Google Scholar
Peng T, Gong J, Jin Y, Zhou Y, Tong R, Wei X, et al. Inhibitors of phosphodiesterase as cancer therapeutics. Eur J Med Chem. 2018;150:742–56.
Article
CAS
Google Scholar
Isacoff WH, Bendetti JK, Barstis JJ, Jazieh AR, Macdonald JS, Philip PA. Phase II trial of infusional fluorouracil, leucovorin, mitomycin, and dipyridamole in locally advanced unresectable pancreatic adenocarcinoma: SWOG S9700. J Clin Oncol. 2007;25(13):1665–9.
Article
CAS
Google Scholar
Mishra RR, Belder N, Ansari SA, Kayhan M, Bal H, Raza U, et al. Reactivation of cAMP Pathway by PDE4D inhibition represents a novel druggable axis for overcoming tamoxifen resistance in er-positive breast cancer. Clin Cancer Res. 2018;24(8):1987–2001.
Article
CAS
Google Scholar
Sun B, Mason S, Wilson RC, Hazard SE, Wang Y, Fang R, et al. Inhibition of the transcriptional kinase CDK7 overcomes therapeutic resistance in HER2-positive breast cancers. Oncogene. 2020;39(1):50–63.
Article
CAS
Google Scholar
Longo J, Mullen PJ, Yu R, van Leeuwen JE, Masoomian M, Woon DTS, et al. An actionable sterol-regulated feedback loop modulates statin sensitivity in prostate cancer. Mol Metab. 2019;25:119–30.
Article
CAS
Google Scholar
Pandyra A, Mullen PJ, Kalkat M, Yu R, Pong JT, Li Z, et al. Immediate utility of two approved agents to target both the metabolic mevalonate pathway and its restorative feedback loop. Cancer Res. 2014;74(17):4772–82.
Article
CAS
Google Scholar
Venkatesh PK, Pattillo CB, Branch B, Hood J, Thoma S, Illum S, et al. Dipyridamole enhances ischaemia-induced arteriogenesis through an endocrine nitrite/nitric oxide-dependent pathway. Cardiovasc Res. 2010;85(4):661–70.
Article
CAS
Google Scholar
MacNeil IA, Burns DJ, Rich BE, Soltani SM, Kharbush S, Osterhaus NG, et al. New HER2-negative breast cancer subtype responsive to anti-HER2 therapy identified. J Cancer Res Clin Oncol. 2020;146(3):605–19.
Article
CAS
Google Scholar
Mezni E, Vicier C, Guerin M, Sabatier R, Bertucci F, Gonçalves A. New therapeutics in HER2-positive advanced breast cancer: towards a change in clinical practices? pi. Cancers (Basel). 2020;12(6):1573.
Article
CAS
Google Scholar
Walz A, Ugolkov A, Chandra S, Kozikowski A, Carneiro BA, O’Halloran TV, et al. Molecular pathways: revisiting glycogen synthase kinase-3β as a target for the treatment of cancer. Clin Cancer Res. 2017;23(8):1891–7.
Article
CAS
Google Scholar
Duda P, Akula SM, Abrams SL, Steelman LS, Martelli AM, Cocco L, et al. Targeting GSK3 and associated signaling pathways involved in cancer. Cells. 2020;9(5):1110.
Article
CAS
Google Scholar
Li S, Li S, Sun Y, Li L. The expression of beta-catenin in different subtypes of breast cancer and its clinical significance. Tumour Biol. 2014;35(8):7693–8.
Article
CAS
Google Scholar
Liao S, Gan L, Qin W, Liu C, Mei Z. Inhibition of GSK3 and MEK induced cancer stem cell generation via the Wnt and MEK signaling pathways. Oncol Rep. 2018;40(4):2005–13.
CAS
Google Scholar
Chiarini F, Evangelisti C, McCubrey JA, Martelli AM. Current treatment strategies for inhibiting mTOR in cancer. Trends Pharmacol Sci. 2015;36(2):124–35.
Article
CAS
Google Scholar
Zou Z, Tao T, Li H, Zhu X. mTOR signaling pathway and mTOR inhibitors in cancer: progress and challenges. Cell Biosci. 2020;10:31.
Article
Google Scholar
Baselga J, Campone M, Piccart M, Burris HA 3rd, Rugo HS, Sahmoud T, et al. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med. 2012;366(6):520–9.
Article
CAS
Google Scholar
Hurvitz SA, Andre F, Jiang Z, Shao Z, Mano MS, Neciosup SP, et al. Combination of everolimus with trastuzumab plus paclitaxel as first-line treatment for patients with HER2-positive advanced breast cancer (BOLERO-1): a phase 3, randomised, double-blind, multicentre trial. Lancet Oncol. 2015;16(7):816–29.
Article
CAS
Google Scholar
Toi M, Shao Z, Hurvitz S, Tseng LM, Zhang Q, Shen K, et al. Efficacy and safety of everolimus in combination with trastuzumab and paclitaxel in Asian patients with HER2+ advanced breast cancer in BOLERO-1. Breast Cancer Res. 2017;19(1):47.
Article
Google Scholar
Azoulay-Alfaguter I, Elya R, Avrahami L, Katz A, Eldar-Finkelman H. Combined regulation of mTORC1 and lysosomal acidification by GSK-3 suppresses autophagy and contributes to cancer cell growth. Oncogene. 2015;34(35):4613–23.
Article
CAS
Google Scholar
Zhang HH, Lipovsky AI, Dibble CC, Sahin M, Manning BD. S6K1 regulates GSK3 under conditions of mTOR-dependent feedback inhibition of Akt. Mol Cell. 2006;24(2):185–97.
Article
CAS
Google Scholar
Beurel E, Jope RS. Differential regulation of STAT family members by glycogen synthase kinase-3. J Biol Chem. 2008;283(32):21934–44.
Article
CAS
Google Scholar
Zhou J, Wulfkuhle J, Zhang H, Gu P, Yang Y, Deng J, et al. Activation of the PTEN/mTOR/STAT3 pathway in breast cancer stem-like cells is required for viability and maintenance. Proc Natl Acad Sci U S A. 2007;104(41):16158–63.
Article
CAS
Google Scholar
Loibl S, von Minckwitz G, Schneeweiss A, Paepke S, Lehmann A, Rezai M, et al. PIK3CA mutations are associated with lower rates of pathologic complete response to anti-human epidermal growth factor receptor 2 (her2) therapy in primary HER2-overexpressing breast cancer. J Clin Oncol. 2014;32(29):3212–20.
Article
CAS
Google Scholar
Sperinde J, Jin X, Banerjee J, Penuel E, Saha A, Diedrich G, et al. Quantitation of p95HER2 in paraffin sections by using a p95-specific antibody and correlation with outcome in a cohort of trastuzumab-treated breast cancer patients. Clin Cancer Res. 2010;16(16):4226–35.
Article
CAS
Google Scholar
Berns K, Horlings HM, Hennessy BT, Madiredjo M, Hijmans EM, Beelen K, et al. A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer. Cancer Cell. 2007;12(4):395–402.
Article
CAS
Google Scholar
Eichhorn PJ, Gili M, Scaltriti M, Serra V, Guzman M, Nijkamp W, et al. Phosphatidylinositol 3-kinase hyperactivation results in lapatinib resistance that is reversed by the mTOR/phosphatidylinositol 3-kinase inhibitor NVP-BEZ235. Cancer Res. 2008;68(22):9221–30.
Article
CAS
Google Scholar
Ritter CA, Perez-Torres M, Rinehart C, Guix M, Dugger T, Engelman JA, et al. Human breast cancer cells selected for resistance to trastuzumab in vivo overexpress epidermal growth factor receptor and ErbB ligands and remain dependent on the ErbB receptor network. Clin Cancer Res. 2007;13(16):4909–19.
Article
CAS
Google Scholar
Shattuck DL, Miller JK, Carraway KL 3rd, Sweeney C. Met receptor contributes to trastuzumab resistance of Her2-overexpressing breast cancer cells. Cancer Res. 2008;68(5):1471–7.
Article
CAS
Google Scholar
Yang L, Li Y, Shen E, Cao F, Li L, Li X, et al. NRG1-dependent activation of HER3 induces primary resistance to trastuzumab in HER2-overexpressing breast cancer cells. Int J Oncol. 2017;51(5):1553–62.
Article
CAS
Google Scholar
Varadan V, Gilmore H, Miskimen KL, Tuck D, Parsai S, Awadallah A, et al. Immune signatures following single dose trastuzumab predict pathologic response to preoperativetrastuzumab and chemotherapy in HER2-positive early breast cancer. Clin Cancer Res. 2016;22(13):3249–59.
Article
CAS
Google Scholar
Chaganty BKR, Qiu S, Gest A, Lu Y, Ivan C, Calin GA, et al. Trastuzumab upregulates PD-L1 as a potential mechanism of trastuzumab resistance through engagement of immune effector cells and stimulation of IFNgamma secretion. Cancer Lett. 2018;430:47–56.
Article
CAS
Google Scholar
Schmidt M, Bohm D, von Torne C, Steiner E, Puhl A, Pilch H, et al. The humoral immune system has a key prognostic impact in node-negative breast cancer. Cancer Res. 2008;68(13):5405–13.
Article
CAS
Google Scholar
Choi JH, Jeon CW, Kim YO, Jung S. Pathological complete response to neoadjuvant trastuzumab and pertuzumab therapy is related to human epidermal growth factor receptor 2 (HER2) amplification level in HER2-amplified breast cancer. Med (Baltimore). 2020;99(46):e23053.
Article
CAS
Google Scholar
Greenwell K, Hussain L, Lee D, Bramlage M, Bills G, Mehta A, et al. Complete pathologic response rate to neoadjuvant chemotherapy increases with increasing HER2/CEP17 ratio in HER2 overexpressing breast cancer: analysis of the National Cancer Database (NCDB). Breast Cancer Res Treat. 2020;181(2):249–54.
Article
CAS
Google Scholar
Singer CF, Tan YY, Fitzal F, Steger GG, Egle D, Reiner A, et al. Pathological complete response to neoadjuvant trastuzumab is dependent on HER2/CEP17 ratio in HER2-amplified early breast cancer. Clin Cancer Res. 2017;23(14):3676–83.
Article
CAS
Google Scholar
Allahham M, Lerman A, Atar D, Birnbaum Y. Why not dipyridamole: a Review of current guidelines and re-evaluation of utility in the modern era. Cardiovasc Drugs Ther. 2022;36(3):525–32.
Harker LA, Kadatz RA. Mechanism of action of dipyridamole. Thromb Res Suppl. 1983;4:39–46.
Article
CAS
Google Scholar
Spano D, Marshall JC, Marino N, De Martino D, Romano A, Scoppettuolo MN, et al. Dipyridamole prevents triple-negative breast-cancer progression. Clin Exp Metastasis. 2013;30(1):47–68.
Article
CAS
Google Scholar
Wang C, Schwab LP, Fan M, Seagroves TN, Buolamwini JK. Chemoprevention activity of dipyridamole in the MMTV-PyMT transgenic mouse model of breast cancer. Cancer Prev Res (Phila). 2013;6(5):437–47.
Article
CAS
Google Scholar
Barone I, Giordano C, Bonofiglio D, Andò S, Catalano S. Phosphodiesterase type 5 and cancers: progress and challenges. Oncotarget. 2017;8(58):99179–202.
Article
Google Scholar
Ge SM, Zhan DL, Zhang SH, Song LQ, Han WW. Reverse screening approach to identify potential anti-cancer targets of dipyridamole. Am J Transl Res. 2016;8(12):5187–98.
CAS
Google Scholar