13. Uray IP, Brown PH (2011) Chemoprevention of hormone receptor-negative breast cancer: new approaches needed. Recent Results Cancer Res 188: 147–162. 14. Brognard J, Clark AS, Ni Y, Dennis PA (2001) Akt/protein kinase B is constitutively active in non-small cell lung cancer cells and promotes cellular survival and resistance to chemotherapy and radiation. Cancer Res 61: 3986–3997. 15. Campbell RA, Bhat-Nakshatri P, Patel NM, Constantinidou D, Ali S, et al. (2001) Phosphatidylinositol 3-kinase/AKT-mediated activation of estrogen receptor alpha: a new model for anti-estrogen resistance. J Biol Chem. 16. Clark AS, West K, Streicher S, Dennis PA (2002) Constitutive and inducible Akt activity promotes resistance to chemotherapy, trastuzumab, or tamoxifen in breast cancer cells. Mol Cancer Ther 1: 707–717. 17. Guo JP, Shu SK, Esposito NN, Coppola D, Koomen JM, et al. (2010) IKKepsilon phosphorylation of estrogen receptor alpha Ser-167 and contribu- tion to tamoxifen resistance in breast cancer. J Biol Chem 285: 3676–3684. 18. Sun M, Paciga JE, Feldman RI, Yuan Z, Coppola D, et al. (2001) Phosphatidylinositol-3-OH Kinase (PI3K)/AKT2, activated in breast cancer, regulates and is induced by estrogen receptor alpha (ERalpha) via interaction between ERalpha and PI3K. Cancer Res 61: 5985–5991. 19. Kawakami M, Koya K, Ukai T, Tatsuta N, Ikegawa A, et al. (1998) Structure- activity of novel rhodacyanine dyes as antitumor agents. J Med Chem 41: 130–142. Rhodacyanine Derivative Kills Resistant Cancers 20. Koren J, Jinwal UK, Jin Y, O’Leary J, Jones JR, et al. (2010) Facilitating Akt clearance via manipulation of Hsp70 activity and levels. J Biol Chem. 21. Gabrielli D, Belisle E, Severino D, Kowaltowski AJ, Baptista MS (2004) Binding, aggregation and photochemical properties of methylene blue in mitochondrial suspensions. Photochem Photobiol 79: 227–232. 22. Rousaki A, Miyata Y, Jinwal UK, Dickey CA, Gestwicki JE, et al. (2011) Allosteric Drugs: The Interaction of Antitumor Compound MKT-077 with Human Hsp70 Chaperones. J Mol Biol. 23. Jinwal UK, Miyata Y, Koren J, 3rd, Jones JR, Trotter JH, et al. (2009) Chemical manipulation of hsp70 ATPase activity regulates tau stability. J Neurosci 29: 12079–12088. 24. Leu JI, Pimkina J, Frank A, Murphy ME, George DL (2009) A small molecule inhibitor of inducible heat shock protein 70. Mol Cell 36: 15–27. 25. Leu JI, Pimkina J, Pandey P, Murphy ME, George DL (2011) HSP70 inhibition by the small-molecule 2-phenylethynesulfonamide impairs protein clearance pathways in tumor cells. Mol Cancer Res 9: 936–947. 26. Dickey CA, Koren J, Zhang YJ, Xu YF, Jinwal UK, et al. (2008) Akt and CHIP coregulate tau degradation through coordinated interactions. Proc Natl Acad Sci U S A 105: 3622–3627. 27. Qian SB, McDonough H, Boellmann F, Cyr DM, Patterson C (2006) CHIP- mediated stress recovery by sequential ubiquitination of substrates and Hsp70. Nature 440: 551–555. PLoS ONE | www.plosone.org 8 April 2012 | Volume 7 | Issue 4 | e35566