Breast cancer: facts and figures 2017–2018. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/breast-cancer-facts-and-figures/breast-cancer-facts-and-figures-2017-2018.pdf.
Sagun Parakh, Hui K. Gan, Adam C. Parslow, Ingrid J.G. Burvenich, Antony W. Burgess, Andrew M. Scott. Evolution of anti-HER2 therapies for cancer treatment. Cancer Treat Rev.2017;59:1-21.
Zanardi E, Bregni G, de Braud F. Di Cosimo S. Semin. Better together: targeted combination therapies in breast cancer. Oncol.2015;42:887–95.
Ford ES, Li C, Zhao G. Prevalence and correlates of metabolic syndrome based on a harmonious definition among adults in the US. J Diabetes.2010;2:180–93.
PubMed
Google Scholar
Boyle P, Boniol M, Koechlin A, et al. Diabetes and breast cancer risk: a meta-analysis. Br J Cancer.2012;107:1608–17.
CAS
PubMed
PubMed Central
Google Scholar
Ferguson RD, Gallagher EJ, Cohen D, Tobin-Hess A, Alikhani N, Novosyadly R, Haddad N, Yakar S, LeRoith D. Hyperinsulinemia promotes metastasis to the lung in a mouse model of Her2-mediated breast cancer. Endocr Relat Cancer. 2013;20:391–401.
CAS
PubMed
PubMed Central
Google Scholar
Park J, Morley TS, Kim M, Clegg DJ, Scherer PE. Obesity and cancer-mechanisms underlying tumor progression and recurrence. Nat Rev Endocrinol. 2014;10:455–65.
CAS
PubMed
PubMed Central
Google Scholar
Bowker SL, Majumdar SR, Veugelers P, Johnson JA. Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin. Diabetes Care. 2006;29:254–8.
PubMed
Google Scholar
Thakkar B, Aronis KN, Vamvini MT, Shields K, Mantzoros CS. Metformin and sulfonylureas in relation to cancer risk in type II diabetes patients: a meta-analysis using primary data of published studies. Metabolism. 2013;62:922–34.
CAS
PubMed
Google Scholar
Sonnenblick A, Agbor-Tarh D, Bradbury I, Di Cosimo S, Azim HA Jr, Fumagalli D, Sarp S, Wolff AC, Andersson M, Kroep J, Cufer T, Simon SD, Salman P, Toi M, Harris L, Gralow J, Keane M, Moreno-Aspitia A, Piccart-Gebhart M, de Azambuja E. Impact of diabetes, insulin, and metformin use on the outcome of patients with human epidermal growth factor receptor 2-positive primary breast cancer: analysis from the ALTTO phase III randomized trial. J Cin Oncol.2017;35:1421–9.
CAS
Google Scholar
Kim HJ, Kwon H, Lee JW, Kim HJ, Lee SB, Park HS, Sohn G, Lee Y, Koh BS, Yu JH, Son BH, Ahn SH. Metformin increases survival in hormone receptor-positive, HER2-positive breast cancer patients with diabetes. Breast Cancer Res. 2015;17:64.
PubMed
PubMed Central
Google Scholar
He X, Esteva FJ, Ensor J, Hortobagyi GN, Lee MH, Yeung SC. Metformin and thiazolidinediones are associated with improved breast cancer-specific survival of diabetic women with HER2+ breast cancer. Ann Oncol. 2012;23:1771–80.
CAS
PubMed
Google Scholar
Jiralerspong S, Palla SL, Giordano SH, Meric-Bernstam F, Liedtke C, Barnett CM, Hsu L, Hung MC, Hortobagyi GN, Gonzalez-Angulo AM. Metformin and pathologic complete responses to neoadjuvant chemotherapy in diabetic patients with breast cancer. J Clin Oncol. 2009;27:3297–302.
CAS
PubMed
PubMed Central
Google Scholar
Guo Z, Zhao M, Howard EW, Zhao Q, Parris AB, Ma Z, Yang X. Phenformin inhibits growth and epithelial-mesenchymal transition of ErbB2-overexpressing breast cancer cells through targeting the IGF1R pathway. Oncotarget. 2017;8:60342–57.
PubMed
PubMed Central
Google Scholar
Parris AB, Zhao Q, Howard EW, Zhao M, Ma Z, Yang X. Buformin inhibits the stemness of erbB-2-overexpressing breast cancer cells and premalignant mammary tissues of MMTV-erbB-2 transgenic mice. J Exp Clin Cancer Res.2017;36:28.
PubMed
PubMed Central
Google Scholar
Alimova IN, Liu B, Fan Z, Edgerton SM, Dillon T, Lind SE, Thor AD. Metformin inhibits breast cancer cell growth, colony formation and induces cell cycle arrest in vitro. Cell Cycle. 2009;8:909–15.
CAS
PubMed
Google Scholar
Za'tara G, Bar-Tana J, Kalderon B, Suter M, Morad E, Samovski D, Neumann D, Hertz R. AMPK activation by long chain fatty acyl analogs. Biochem Pharmacol. 2008;76:1263–75.
CAS
PubMed
Google Scholar
Zatara G, Hertz R, Shaked M, Mayorek N, Morad E, Grad E, Cahan A, Danenberg HD, Unterman TG, Bar-Tana J. Suppression of FoxO1 activity by long-chain fatty acyl analogs. Diabetes. 201;60:1872-81.
Kalderon B, Azazmeh N, Azulay N, Vissler N, Valitsky M, Bar-Tana J. Suppression of adipose lipolysis by long-chain fatty acid analogs. Journal of Lipid Research. 2012;53:868–78.
CAS
PubMed
PubMed Central
Google Scholar
Valitsky M, Hoffman A, Unterman T, Bar-Tana J. Insulin sensitizer prevents and ameliorates experimental type 1 diabetes. Am J Physiol Endocrinol Metab. 2017;313:E672–80.
PubMed
Google Scholar
Algamas-Dimantov A, Yehuda-Shnaidman E, Hertz R, Peri I, Bar-Tana J, Schwartz B. Prevention of diabetes-promoted colorectal cancer by (n-3) polyunsaturated fatty acids and (n-3) PUFA mimetic. Oncotarget.2014;5:9851–63.
PubMed
PubMed Central
Google Scholar
Gluschnaider U, Hertz R, Ohayon S, Smeir E, Smets M, Pikarsky E, Bar-Tana J. Long-chain fatty acid analogues suppress breast tumorigenesis and progression. Cancer Res. 2014;74:6991–7002.
CAS
PubMed
Google Scholar
Longati P, Jia X, Eimer J, Wagman A, Witt MR, Rehnmark S, Verbeke C, Toftgård R, Löhr M, Heuchel RL. 3D pancreatic carcinoma spheroids induce a matrix-rich, chemoresistant phenotype offering a better model for drug testing. BMC Cancer. 2013;13:95.
CAS
PubMed
PubMed Central
Google Scholar
Atiq R, Hertz R, Eldad S, Smeir E, Bar-Tana J. Suppression of B-Raf(V600E) cancers by MAPK hyper-activation. Oncotarget. 2016;7:18694–704.
PubMed
PubMed Central
Google Scholar
Saada A, Bar-Meir M, Belaiche C, Miller C, Elpeleg O. Evaluation of enzymatic assays and compounds affecting ATP production in mitochondrial respiratory chain complex I deficiency. Anal Biochem. 2004;335:66–72.
CAS
PubMed
Google Scholar
Bar-Tana J, Ben-Shoshan S, Blum J, Migron Y, Hertz R, Pill J, Rose-Khan G, Witte EC. Synthesis and hypolipidemic and antidiabetogenic activities of beta,beta,beta',beta'-tetrasubstituted, long-chain dioic acids. J Med Chem. 1989;32:2072-2084.
Muller WJ, Sinn E, Pattengale PK, Wallace R, Leder P. Single-step induction of mammary adenocarcinoma in transgenic mice bearing the activated c-neu oncogene. Cell. 1988;54:105–15.
CAS
PubMed
Google Scholar
Guy CT, Webster MA, Schaller M, Parsons TJ, Cardiff RD, Muller WJ. Expression of the Neu protooncogene in the mammary epithelium of transgenic mice induces metastatic disease. Proc Natl Acad Sci USA. 1992;89:10578–82.
CAS
PubMed
Google Scholar
Subik K, Lee JF, Baxter L, Strzepek T, Costello D, Crowley P, Xing L, Hung MC, Bonfiglio T, Hicks DG, Tang P. The expression patterns of ER, PR, HER2, CK5/6, EGFR, Ki-67 and AR by immunohistochemical analysis in breast cancer cell lines. Breast Cancer (Auckl). 2010;4:35–41.
PubMed
PubMed Central
Google Scholar
Lee CH, Yu CC, Wang BY, Chang WW. Tumorsphere as an effective in vitro platform for screening anti-cancer stem cell drugs. Oncotarget. 2016;7:1215–26.
PubMed
Google Scholar
Nagy P, Vereb G, Sebestyén Z, Horváth G, Lockett SJ, Damjanovich S, Park JW, Jovin TM, Szöllosi J. Lipid rafts and the local density of ErbB proteins influence the biological role of homo- and heteroassociations of ErbB2. J Cell Sci. 2002;115:4251–62.
CAS
PubMed
Google Scholar
Babina IS, Donatello S, Nabi IR, Hopkins AM. Lipid rafts as master regulators of breast cancer cell function. In: Breast cancer - carcinogenesis, cell growth and signalling pathways. Editors: M. Gunduz, E. Gunduz. InTech, ISBN 978-953-307-714-7. 2011;401-428.
Nourissat P, Travert M, Chevanne M, Tekpli X, Rebillard A, Le Moigne-Müller G, Rissel M, Cillard J, Dimanche-Boitrel MT, Lagadic-Gossmann D, Sergent O. Ethanol induces oxidative stress in primary rat hepatocytes through the early involvement of lipid raft clustering. Hepatology. 2008;47:59–70.
CAS
PubMed
Google Scholar
Santos AL, Preta G. Lipids in the cell: organisation regulates function. Cell Mol Life Sci. 2018;75:1909–27.
CAS
PubMed
Google Scholar
Demetriades C, Plescher M, Teleman AA. Lysosomal recruitment of TSC2 is a universal response to cellular stress. Nat Commun. 2016;7:10662.
CAS
PubMed
PubMed Central
Google Scholar
Atamna H, Nguyen A, Schultz C, Boyle K, Newberry J, Kato H, Ames BN. Methylene blue delays cellular senescence and enhances key mitochondrial biochemical pathways. FASEB Journal. 2008;22:703–12.
CAS
PubMed
Google Scholar
Wheaton WW, Weinberg SE, Hamanaka RB, Soberanes S, Sullivan LB, Anso E, Glasauer A, Dufour E, Mutlu GM, Budigner GS, Chandel NS. Metformin inhibits mitochondrial complex I of cancer cells to reduce tumorigenesis. Elife. 2014;3:e02242..
PubMed
PubMed Central
Google Scholar
Aguer C, Gambarotta D, Mailloux RJ, Moffat C, Dent R, McPherson R, Harper ME. Galactose enhances oxidative metabolism and reveals mitochondrial dysfunction in human primary muscle cells. PLoS One. 2011;6:e28536.
CAS
PubMed
PubMed Central
Google Scholar
Birsoy K, Wang T, Chen WW, Freinkman E, Abu-Remaileh M, Sabatini DM. An essential role of the mitochondrial electron transport chain in cell proliferation is to enable aspartate synthesis. Cell. 2015;162:540–51.
CAS
PubMed
PubMed Central
Google Scholar
Sullivan LB, Gui DY, Hosios AM, Bush LN. Freinkman E, Vander HeidenMG. Supporting aspartate biosynthesis is an essential function of respiration in proliferating cells. Cell.2015;162:552–63.
CAS
PubMed
PubMed Central
Google Scholar
Sullivan LB, Luengo A, Danai LV, Bush LN, Diehl FF, Hosios AM, Lau AN, Elmiligy S, Malstrom S, Lewis CA, Vander Heiden MG. Aspartate is an endogenous metabolic limitation for tumour growth. Nat Cell Biol. 2018;20:782–8.
CAS
PubMed
PubMed Central
Google Scholar
Garcia-Bermudez J, Baudrier L, La K, Zhu XG, Fidelin J, Sviderskiy VO, Papagiannakopoulos T, Molina H, Snuderl M, Lewis CA, Possemato RL, Birsoy K. Aspartate is a limiting metabolite for cancer cell proliferation under hypoxia and in tumours. Nat Cell Biol. 2018;20:775–81.
CAS
PubMed
PubMed Central
Google Scholar
Saxton RA, Sabatini DM. mTOR signaling in growth, metabolism, and disease. Cell. 2017;168:960–76.
CAS
PubMed
PubMed Central
Google Scholar
Rodrik-Outmezguine VS, Chandarlapaty S, Pagano NC, Poulikakos PI, Scaltriti M, Moskatel E, Baselga J, Guichard S, Rosen N. mTOR kinase inhibition causes feedback-dependent biphasic regulation of AKT signaling. Cancer Discov. 2011;1:248–59.
CAS
PubMed
PubMed Central
Google Scholar
Chandarlapaty S, Sawai A, Scaltriti M, Rodrik-Outmezguine V, Grbovic-Huezo O, Serra V, Majumder PK, Baselga J, Rosen N. AKT inhibition relieves feedback suppression of receptor tyrosine kinase expression and activity. Cancer Cell. 2011;19:58–71.
CAS
PubMed
PubMed Central
Google Scholar
O'Reilly KE, Rojo F, She QB, Solit D, Mills GB, Smith D, Lane H, Hofmann F, Hicklin DJ, Ludwig DL, Baselga J, Rosen N. mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt. Cancer Res. 2006;66:1500–8.
CAS
PubMed
PubMed Central
Google Scholar
Carracedo A, Ma L, Teruya-Feldstein J, Rojo F, Salmena L, Alimonti A, Egia A, Sasaki AT, Thomas G, Kozma SC, Papa A, Nardella C, Cantley LC, Baselga J, Pandolfi PP. Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer. J Clin Invest. 2008;118:3065–74.
CAS
PubMed
PubMed Central
Google Scholar
Chandarlapaty S. Negative feedback and adaptive resistance to the targeted therapy of cancer. Cancer Discov. 2012;2:311–9.
CAS
PubMed
PubMed Central
Google Scholar
Bayat Mokhtari R, Homayouni TS, Baluch N, Morgatskaya E, Kumar S, Das B, Yeger H. Combination therapy in combating cancer. Oncotarget. 2017;8:38022–43.
PubMed
Google Scholar
Kase ET, Nikolić N, Bakke SS, Bogen KK, Aas V, Thoresen GH, Rustan AC. Remodeling of oxidative energy metabolism by galactose improves glucose handling and metabolic switching in human skeletal muscle cells. PLoS One.2013;8:e59972.
CAS
PubMed
PubMed Central
Google Scholar
Menezes SV, Sahni S, Kovacevic Z, Richardson DR. J. Interplay of the iron-regulated metastasis suppressor NDRG1 with epidermal growth factor receptor (EGFR) and oncogenic signaling. Biol Chem. 2017;292:12772–82.
CAS
Google Scholar
Mi L, Zhu F, Yang X, Lu J, Zheng Y, Zhao Q, Wen X, Lu A, Wang M, Zheng M, Ji J, Sun J. The metastatic suppressor NDRG1 inhibits EMT, migration and invasion through interaction and promotion of caveolin-1 ubiquitylation in human colorectal cancer cells. Oncogene.2017;36:4323–35.
CAS
PubMed
PubMed Central
Google Scholar
Fang BA, Kovačević Ž, Park KC, Kalinowski DS, Jansson PJ, Lane DJ, Sahni S, Richardson DR. Molecular functions of the iron-regulated metastasis suppressor, NDRG1, and its potential as a molecular target for cancer therapy. Biochim Biophys Acta. 1845;2014:1–19.
Google Scholar
Pernas S, Dorca J, Álvarez-López I, et al. Safety and efficacy of neoadjuvant metformin with trastuzumab and chemotherapy in women with HER2-positive early breast cancer: a randomized, open-label, multicenter, phase 2 trial. San Antonio Breast Cancer Symposium (SABCS).2017..
Kang C, LeRoith D, Gallagher EJ. Diabetes, obesity, and breast cancer. Endocrinology. 2018;159:3801–12.
CAS
PubMed
PubMed Central
Google Scholar
Howell JJ, Ricoult SJ, Ben-Sahra I, Manning BD. A growing role for mTOR in promoting anabolic metabolism. Biochem Soc Trans. 2013;41:906–12.
CAS
PubMed
Google Scholar