Review
Enhancing FTS (Salirasib) efficiency via combinatorial treatment
Eya Wolfson,
Eran Schmukler,
Sari Trangle Schokoroy,
Yoel Kloog,
Ronit Pinkas-Kramarski,
Eya Wolfson
Department of Neurobiology, Tel-Aviv University, Ramat-Aviv, Israel
Search for more papers by this authorEran Schmukler
Department of Neurobiology, Tel-Aviv University, Ramat-Aviv, Israel
Search for more papers by this authorSari Trangle Schokoroy
Department of Neurobiology, Tel-Aviv University, Ramat-Aviv, Israel
Search for more papers by this authorYoel Kloog
Department of Neurobiology, Tel-Aviv University, Ramat-Aviv, Israel
Search for more papers by this authorCorresponding Author
Ronit Pinkas-Kramarski
Department of Neurobiology, Tel-Aviv University, Ramat-Aviv, Israel
To whom correspondence should be addressed (email [email protected])Search for more papers by this author
Eya Wolfson,
Eran Schmukler,
Sari Trangle Schokoroy,
Yoel Kloog,
Ronit Pinkas-Kramarski,
Eya Wolfson
Department of Neurobiology, Tel-Aviv University, Ramat-Aviv, Israel
Search for more papers by this authorEran Schmukler
Department of Neurobiology, Tel-Aviv University, Ramat-Aviv, Israel
Search for more papers by this authorSari Trangle Schokoroy
Department of Neurobiology, Tel-Aviv University, Ramat-Aviv, Israel
Search for more papers by this authorYoel Kloog
Department of Neurobiology, Tel-Aviv University, Ramat-Aviv, Israel
Search for more papers by this authorCorresponding Author
Ronit Pinkas-Kramarski
Department of Neurobiology, Tel-Aviv University, Ramat-Aviv, Israel
To whom correspondence should be addressed (email [email protected])Search for more papers by this authorAbstract
The Ras oncogene transmits signals, which regulate various cellular processes including cell motility, differentiation, growth and death. Since Ras signalling is abnormally activated in more than 30% of human cancers, Ras and its downstream signalling pathways are considered good targets for therapeutic interference. Ras is post-translationally modified by the addition of a farnesyl group, which permits its attachment to the plasma membrane. Exploiting this knowledge, a synthetic Ras inhibitor, S-trans, trans-farnesylthiosalicylic acid (FTS; Salirasib), was developed. FTS resembles the farnesylcysteine group of Ras, and acts as an effective Ras antagonist. In the present review, the effect of FTS in combination with various other drugs, as tested in vitro and in vivo, and its therapeutic potential are discussed. As reviewed, FTS cooperates with diverse therapeutic agents, which significantly improves treatment outcome. Therefore, combinations of FTS with other agents have a potential to serve as anti-cancer or anti-inflammatory therapies.
References
- Aizman, E., Mor, A., Chapman, J., Assaf, Y. and Kloog, Y. (2010) The combined treatment of Copaxone and Salirasib attenuates experimental autoimmune encephalomyelitis (EAE) in mice. J. Neuroimmunol. 229, 192–203
- Aizman, E., Mor, A., Levy, A., George, J. and Kloog, Y. (2012) Ras inhibition by FTS attenuates brain tumor growth in mice by direct antitumor activity and enhanced reactivity of cytotoxic lymphocytes. Oncotarget 3, 144–157
- Bates, P.J., Kahlon, J.B., Thomas, S.D., Trent, J.O. and Miller, D.M. (1999) Antiproliferative activity of G-rich oligonucleotides correlates with protein binding. J. Biol. Chem. 274, 26369–26377
- Beaudin, S.G., Robilotto, S. and Welsh, J. (2015) Comparative regulation of gene expression by 1,25-dihydroxyvitamin D in cells derived from normal mammary tissue and breast cancer. J. Steroid Biochem. Mol. Biol. 148, 96–102
- Beiner, M.E., Niv, H., Haklai, R., Elad-Sfadia, G., Kloog, Y. and Ben-Baruch, G. (2006) Ras antagonist inhibits growth and chemosensitizes human epithelial ovarian cancer cells. Int. J. Gynecol. Cancer 16(1), 200–206
- Biran, A., Brownstein, M., Haklai, R. and Kloog, Y. (2011) Downregulation of survivin and aurora A by histone deacetylase and RAS inhibitors: a new drug combination for cancer therapy. Int. J. Cancer 128, 691–701
- Blum, R., Jacob-Hirsch, J., Amariglio, N., Rechavi, G. and Kloog, Y. (2005) Ras inhibition in glioblastoma down-regulates hypoxia-inducible factor-1alpha, causing glycolysis shutdown and cell death. Cancer Res. 65, 999–1006
- Bos, J.L. (1989) ras oncogenes in human cancer: a review. Cancer Res. 49, 4682–4689
- Byun, J.Y., Yoon, C.H., An, S., Park, I.C., Kang, C.M., Kim, M.J. and Lee, S.J. (2009) The Rac1/MKK7/JNK pathway signals upregulation of Atg5 and subsequent autophagic cell death in response to oncogenic Ras. Carcinogenesis 30, 1880–1888
- Borthakur, G.,.Ravandi, F., O'Brien, S., Williams, B. and Giles, F. (2007) Phase I study of s-trans, trans-farnesylthiosalicylic acid (FTS), a novel oral Ras inhibitor, in patients with refractory hematologic malignancies. J. Clin. Oncol. 25, 7071
- Charette, N., De Saeger, C., Horsmans, Y., Leclercq, I. and Starkel, P. (2013) Salirasib sensitizes hepatocarcinoma cells to TRAIL-induced apoptosis through DR5 and survivin-dependent mechanisms. Cell Death Dis. 4, e471
- Chen, Y., Zhang, X., Lu, J., Huang, Y., Li, J. and Li, S. (2014) Targeted delivery of curcumin to tumors via PEG-derivatized FTS-based micellar system. AAPS J. 16, 600–608
- Christian, S., Pilch, J., Akerman, M.E., Porkka, K., Laakkonen, P. and Ruoslahti, E. (2003) Nucleolin expressed at the cell surface is a marker of endothelial cells in angiogenic blood vessels. J. Cell Biol. 163, 871–878
- Codogno, P. and Meijer, A.J. (2005) Autophagy and signaling: their role in cell survival and cell death. Cell Death Differ. 12(Suppl 2), 1509–1518
- Coussens, L.M. and Werb, Z. (2002) Inflammation and cancer. Nature 420, 860–867
- de Verdugo, U.R., Selinka, H.C., Huber, M., Kramer, B., Kellermann, J., Hofschneider, P.H. and Kandolf, R. (1995) Characterization of a 100-kilodalton binding protein for the six serotypes of coxsackie B viruses. J Virol 69, 6751–6757
- Degenhardt, K., Mathew, R., Beaudoin, B., Bray, K., Anderson, D., Chen, G., Mukherjee, C., Shi, Y., Gelinas, C., Fan, Y., Nelson, D.A., Jin, S. and White, E. (2006) Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis. Cancer Cell 10, 51–64
- Derenzini, M., Sirri, V., Trere, D. and Ochs, R.L. (1995) The quantity of nucleolar proteins nucleolin and protein B23 is related to cell doubling time in human cancer cells. Lab Invest 73, 497–502
- Destouches, D., El Khoury, D., Hamma-Kourbali, Y., Krust, B., Albanese, P., Katsoris, P., Guichard, G., Briand, J.P., Courty, J. and Hovanessian, A.G. (2008) Suppression of tumor growth and angiogenesis by a specific antagonist of the cell-surface expressed nucleolin. PLoS One 3, e2518
- Di Segni, A., Ben-Baruch, N. and Pinkas-Kramarski, R. (2009) The ErbB family of receptor tyrosine kinases: key regulators in breast cancer and other malignancies. In: Breast cancer: from pathogenesis to potential therapeutic modalities ( A Ben-Baruch, ed.), Transworld Research Network, Kerala, pp 77–105.
- Di Segni, A., Farin, K. and Pinkas-Kramarski, R. (2008) Identification of nucleolin as new ErbB receptors- interacting protein. PLoS One 3, e2310
- Downward, J. (2003) Targeting RAS signalling pathways in cancer therapy. Nature Rev. Cancer 3, 11–22
- Erlich, S., Tal-Or, P., Liebling, R., Blum, R., Karunagaran, D., Kloog, Y. and Pinkas-Kramarski, R. (2006) Ras inhibition results in growth arrest and death of androgen-dependent and androgen-independent prostate cancer cells. Biochem. Pharmacol. 72, 427–436
- Faigenbaum, R., Haklai, R., Ben-Baruch, G. and Kloog, Y. (2013) Growth of poorly differentiated endometrial carcinoma is inhibited by combined action of medroxyprogesterone acetate and the Ras inhibitor Salirasib. Oncotarget 4, 316–328
- Farin, K., Di Segni, A., Mor, A. and Pinkas-Kramarski, R. (2009) Structure-function analysis of nucleolin and ErbB receptors interactions. PLoS One 4, e6128
- Farin, K., Schokoroy, S., Haklai, R., Cohen-Or, I., Elad-Sfadia, G., Reyes-Reyes, M.E., Bates, P.J., Cox, A.D., Kloog, Y. and Pinkas-Kramarski, R. (2011) Oncogenic synergism between ErbB1, nucleolin, and mutant Ras. Cancer Res. 71, 2140–2151
- Fonseca, R., Barlogie, B., Bataille, R., Bastard, C., Bergsagel, P.L., Chesi, M., Davies, F.E., Drach, J., Greipp, P.R., Kirsch, I.R., Kuehl, W.M., Hernandez, J.M., Minvielle, S., Pilarski, L.M., Shaughnessy, J.D., Jr., Stewart, A.K. and Avet-Loiseau, H. (2004) Genetics and cytogenetics of multiple myeloma: a workshop report. Cancer Res. 64, 1546–1558
- Furuta, S., Hidaka, E., Ogata, A., Yokota, S. and Kamata, T. (2004) Ras is involved in the negative control of autophagy through the class I PI3-kinase. Oncogene 23, 3898–3904
- Galzio, R., Rosati, F., Benedetti, E., Cristiano, L., Aldi, S., Mei, S., D'Angelo, B., Gentile, R., Laurenti, G., Cifone, M.G., Giordano, A. and Cimini, A. (2012) Glycosilated nucleolin as marker for human gliomas. J. Cell. Biochem. 113, 571–579
- Gana-Weisz, M., Halaschek-Wiener, J., Jansen, B., Elad, G., Haklai, R. and Kloog, Y. (2002) The Ras inhibitor S-trans,trans-farnesylthiosalicylic acid chemosensitizes human tumor cells without causing resistance. Clin. Cancer Res. 8, 555–565
- Goldberg, L., Israeli, R. and Kloog, Y. (2012) FTS and 2-DG induce pancreatic cancer cell death and tumor shrinkage in mice. Cell Death Dis 3, e284
- Goldshmit, Y., Trangle, S.S., Kloog, Y. and Pinkas-Kramarski, R. (2014) Interfering with the interaction between ErbB1, nucleolin and Ras as a potential treatment for glioblastoma. Oncotarget 5, 8602–8613
- Guha, A., Feldkamp, M.M., Lau, N., Boss, G. and Pawson, A. (1997) Proliferation of human malignant astrocytomas is dependent on Ras activation. Oncogene 15, 2755–2765
- Guo, J.Y., Karsli-Uzunbas, G., Mathew, R., Aisner, S.C., Kamphorst, J.J., Strohecker, A.M., Chen, G., Price, S., Lu, W., Teng, X., Snyder, E., Santanam, U., Dipaola, R.S., Jacks, T., Rabinowitz, J.D. and White, E. (2013) Autophagy suppresses progression of K-ras-induced lung tumors to oncocytomas and maintains lipid homeostasis. Genes Dev 27, 1447–1461
- Haklai, R., Elad-Sfadia, G., Egozi, Y. and Kloog, Y. (2008) Orally administered FTS (salirasib) inhibits human pancreatic tumor growth in nude mice. Cancer Chemoth Pharmacol. 61, 89–96
- Haklai, R., Weisz, M.G., Elad, G., Paz, A., Marciano, D., Egozi, Y., Ben-Baruch, G. and Kloog, Y. (1998) Dislodgment and accelerated degradation of Ras. Biochemistry 37, 1306–1314
- Halaschek-Wiener, J., Kloog, Y., Wacheck, V. and Jansen, B. (2003) Farnesyl thiosalicylic acid chemosensitizes human melanoma in vivo. J. Invest. Dermatol. 120, 109–115
- Khambata-Ford, S., Garrett, C.R., Meropol, N.J., Basik, M., Harbison, C.T., Wu, S., Wong, T.W., Huang, X., Takimoto, C.H., Godwin, A.K., Tan, B.R., Krishnamurthi, S.S., Burris, H.A., 3rd, Poplin, E.A., Hidalgo, M., Baselga, J., Clark, E.A. and Mauro, D.J. (2007) Expression of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab. J. Clin. Oncol. 25, 3230–3237
- Kimmelman, A.C. (2011) The dynamic nature of autophagy in cancer. Genes Dev. 25, 1999–2010
- Kinsella, A.R., Smith, D. and Pickard, M. (1997) Resistance to chemotherapeutic antimetabolites: a function of salvage pathway involvement and cellular response to DNA damage. Br. J. Cancer 75, 935–945
- Kloog, Y., Elad-Sfadia, G., Haklai, R. and Mor, A. (2013) Ras chaperones: new targets for cancer and immunotherapy. Enzymes 33(Pt A), 267–289
- Kraitzer, A., Kloog, Y., Haklai, R. and Zilberman, M. (2011) Composite fiber structures with antiproliferative agents exhibit advantageous drug delivery and cell growth inhibition in vitro. J. Pharm. Sci. 100, 133–149
- LaBonte, M.J., Wilson, P.M., Fazzone, W., Russell, J., Louie, S.G., El-Khoueiry, A., Lenz, H.J. and Ladner, R.D. (2011) The dual EGFR/HER2 inhibitor lapatinib synergistically enhances the antitumor activity of the histone deacetylase inhibitor panobinostat in colorectal cancer models. Cancer Res. 71, 3635–3648
- Laheru, D., Shah, P., Rajeshkumar, N.V., McAllister, F., Taylor, G., Goldsweig, H., Le, D.T., Donehower, R., Jimeno, A., Linden, S., Zhao, M., Song, D., Rudek, M.A. and Hidalgo, M. (2012) Integrated preclinical and clinical development of S-trans, trans-Farnesylthiosalicylic Acid (FTS, Salirasib) in pancreatic cancer. Invest. New Drugs 30, 2391–2399
- Legrand, D., Vigie, K., Said, E., Elass, E., Masson, M., Slomianny, M., Carpentier M, Briand, J., Mazurier, J. and Hovanessian, A. (2004) Surface nucleolin participates in both the binding and endocytosis of lactoferrin in target cells. Eur. J. Biochem./ FEBS 271, 303–317
- Ling, Y., Wang, Z., Wang, X., Zhao, Y., Zhang, W., Wang, X., Chen, L., Huang, Z. and Zhang, Y. (2014) Synthesis and biological evaluation of hybrids from farnesylthiosalicylic acid and hydroxylcinnamic acid with dual inhibitory activities of Ras-related signaling and phosphorylated NF-kappaB. Org. Biomol. Chem. 12, 4517–4530
- Logan, C.Y. and Nusse, R. (2004) The Wnt signaling pathway in development and disease. Annu. Rev. Cell Dev. Biol. 20, 781–810
- Lonn, U. and Lonn, S. (1987) W-7, a calmodulin inhibitor, potentiates dacarbazine cytotoxicity in human neoplastic cells. Int. J. Cancer 39, 638–642
- Mackenzie, G.G., Bartels, L.E., Xie, G., Papayannis, I., Alston, N., Vrankova, K., Ouyang, N. and Rigas, B. (2013) A novel Ras inhibitor (MDC-1016) reduces human pancreatic tumor growth in mice. Neoplasia 15, 1184–1195
- Mancias, J.D. and Kimmelman, A.C. (2011) Targeting autophagy addiction in cancer. Oncotarget 2, 1302–1306
- Marom, M., Haklai, R., Ben-Baruch, G., Marciano, D., Egozi, Y. and Kloog, Y. (1995) Selective inhibition of Ras-dependent cell growth by farnesylthiosalisylic acid. J. Biol. Chem. 270, 22263–22270
- Mashiach-Farkash, E., Rak, R., Elad-Sfadia, G., Haklai, R., Carmeli, S., Kloog, Y. and Wolfson, H.J. (2012) Computer-based identification of a novel LIMK1/2 inhibitor that synergizes with salirasib to destabilize the actin cytoskeleton. Oncotarget 3, 629–639
- Mathew, R., Karantza-Wadsworth, V. and White, E. (2009) Assessing metabolic stress and autophagy status in epithelial tumors. Methods Enzymol. 453, 53–81
- Mologni, L., Brussolo, S., Ceccon, M. and Gambacorti-Passerini, C. (2012) Synergistic effects of combined Wnt/KRAS inhibition in colorectal cancer cells. PloS One 7, e51449
- Mor, A., Aizman, E., Chapman, J. and Kloog, Y. (2013) Immunomodulatory properties of farnesoids: the new steroids? Curr. Med. Chem. 20, 1218–1224
- Mor, A., Aizman, E. and Kloog, Y. (2012) Celecoxib enhances the anti-inflammatory effects of farnesylthiosalicylic acid on T cells independent of prostaglandin E(2) production. Inflammation 35, 1706–1714
- Neeman, R., Abramovitch, S., Sharvit, E., Elad-Sfadia, G., Haklai, R., Kloog, Y. and Reif, S. (2014) Vitamin D and S-farnesylthiosalicylic Acid have a synergistic effect on hepatic stellate cells proliferation. Digest. Dis Sci 59, 2462–2469
- Niv, H., Gutman, O., Henis, Y.I. and Kloog, Y. (1999) Membrane interactions of a constitutively active GFP-Ki-Ras 4B and their role in signaling. Evidence from lateral mobility studies. J. Biol. Chem. 274, 1606–1613
- Normanno, N., Bianco, C., De Luca, A., Maiello, M.R. and Salomon, D.S. (2003) Target-based agents against ErbB receptors and their ligands: a novel approach to cancer treatment. Endocr.-Relat. Cancer 10, 1–21
- Normanno, N., Tejpar, S., Morgillo, F., De Luca, A., Van Cutsem, E. and Ciardiello, F. (2009) Implications for KRAS status and EGFR-targeted therapies in metastatic CRC. Nat. Rev. Clin. Oncol. 6, 519–527
- Pattingre, S., Bauvy, C. and Codogno, P. (2003) Amino acids interfere with the ERK1/2-dependent control of macroautophagy by controlling the activation of Raf-1 in human colon cancer HT-29 cells. J. Biol. Chem. 278, 16667–16674
- Pavek, P. and Smutny, T. (2014) Nuclear receptors in regulation of biotransformation enzymes and drug transporters in the placental barrier. Drug Metab. Rev. 46, 19–32
- Pietras, R.J., Fendly, B.M., Chazin, V.R., Pegram, M.D., Howell, S.B. and Slamon, D.J. (1994) Antibody to HER-2/neu receptor blocks DNA repair after cisplatin in human breast and ovarian cancer cells. Oncogene 9, 1829–1838
- Plowman, S.J. and Hancock, J.F. (2005) Ras signaling from plasma membrane and endomembrane microdomains. Biochim. Biophys. Acta 1746, 274–283
- Rajkumar, S.V., Richardson, P.G., Hideshima, T. and Anderson, K.C. (2005) Proteasome inhibition as a novel therapeutic target in human cancer. J. Clin. Oncol. 23, 630–639
- Ravikumar, B., Sarkar, S., Davies, J.E., Futter, M., Garcia-Arencibia, M., Green-Thompson, Z.W., Jimenez-Sanchez, M., Korolchuk, V.I., Lichtenberg, M., Luo, S., Massey, D.C., Menzies, F.M., Moreau, K., Narayanan, U., Renna, M., Siddiqi, F.H., Underwood, B.R., Winslow, A.R. and Rubinsztein, D.C. (2010) Regulation of mammalian autophagy in physiology and pathophysiology. Physiol. Rev. 90, 1383–1435
- Rotblat, B., Ehrlich, M., Haklai, R. and Kloog, Y. (2008) The Ras inhibitor farnesylthiosalicylic acid (Salirasib) disrupts the spatiotemporal localization of active Ras: a potential treatment for cancer. Methods Enzymol. 439, 467–489
- Roussel, P. and Hernandez-Verdun, D. (1994) Identification of Ag-NOR proteins, markers of proliferation related to ribosomal gene activity. Exp. Cell Res. 214, 465–472
- Santucci, R., Mackley, P.A., Sebti, S. and Alsina, M. (2003) Farnesyltransferase inhibitors and their role in the treatment of multiple myeloma. Cancer Control 10, 384–387
- Schmukler, E., Grinboim, E., Schokoroy, S., Amir, A., Wolfson, E., Kloog, Y. and Pinkas-Kramarski, R. (2013) Ras inhibition enhances autophagy, which partially protects cells from death. Oncotarget 4, 142–152
- Schmukler, E., Kloog, Y. and Pinkas-Kramarski, R. (2014a) Ras and autophagy in cancer development and therapy. Oncotarget. 5, 577–586
- Schmukler, E., Wolfson, E., Haklai, R., Elad-Sfadia, G., Kloog, Y. and Pinkas-Kramarski, R. (2014b) Chloroquine synergizes with FTS to enhance cell growth inhibition and cell death. Oncotarget 5, 173–184
- Schokoroy, S., Juster, D., Kloog, Y. and Pinkas-Kramarski, R. (2013) Disrupting the oncogenic synergism between nucleolin and Ras results in cell growth inhibition and cell death. PloS One 8, e75269
- Slater, A.F. (1993) Chloroquine: mechanism of drug action and resistance in Plasmodium falciparum. Pharmacol. Ther. 57, 203–235
- Smalley, K.S. and Eisen, T.G. (2003) Farnesyl transferase inhibitor SCH66336 is cytostatic, pro-apoptotic and enhances chemosensitivity to cisplatin in melanoma cells. Int. J. Cancer 105, 165–175
- Srivastava, M. and Pollard, H.B. (1999) Molecular dissection of nucleolin's role in growth and cell proliferation: new insights. FASEB J 13, 1911–1922
- Starkel, P., Charette, N., Borbath, I., Schneider-Merck, T., De Saeger, C., Abarca, J., Leclercq, I. and Horsmans, Y. (2012) Ras inhibition in hepatocarcinoma by S-trans-trans-farnesylthiosalicyclic acid: association of its tumor preventive effect with cell proliferation, cell cycle events, and angiogenesis. Mol. Carcinog. 51, 816–825
- Stepanova, V., Lebedeva, T., Kuo, A., Yarovoi, S., Tkachuk, S., Zaitsev, S., Bdeir, K., Dumler, I., Marks, M.S., Parfyonova, Y., Tkachuk, V.A., Higazi, A.A. and Cines, D.B. (2008) Nuclear translocation of urokinase-type plasminogen activator. Blood 112, 100–110
- Storck, S., Shukla, M., Dimitrov, S. and Bouvet, P. (2007) Functions of the histone chaperone nucleolin in diseases. Subcell. Biochem. 41, 125–144
- Storck, S., Thiry, M. and Bouvet, P. (2008) Conditional knockout of nucleolin in DT40 cells reveals the functional redundancy of its RNA binding domains. Biol. Cell 101, 153–167
- Sun, X., Vilar, S. and Tatonetti, N.P. (2013) High-throughput methods for combinatorial drug discovery. Sci. Transl. Med. 5, 205rv201
- Troselj, K.G. and Kujundzic, R.N. (2014) Curcumin in combined cancer therapy. Curr. Pharm. Des 20, 6682–6696
- Ugrinova, I., Monier, K., Ivaldi, C., Thiry, M., Storck, S., Mongelard, F. and Bouvet, P. (2007) Inactivation of nucleolin leads to nucleolar disruption, cell cycle arrest and defects in centrosome duplication. BMC Mol. Biol. 8, 66
- Vogelstein, B. and Kinzler, K.W. (2004) Cancer genes and the pathways they control. Nat. Med. 10, 789–799
- Vojtek, A.B. and Der, C.J. (1998) Increasing complexity of the Ras signaling pathway. J. Biol. Chem. 273, 19925–19928
- Wu, D.M., Zhang, P., Liu, R.Y., Sang, Y.X., Zhou, C., Xu, G.C., Yang, J.L., Tong, A.P. and Wang, C.T. (2014) Phosphorylation and changes in the distribution of nucleolin promote tumor metastasis via the PI3K/Akt pathway in colorectal carcinoma. FEBS Lett. 588, 1921–1929
- Xu, X., Hamhouyia, F., Thomas, S.D., Burke, T.J., Girvan, A.C., McGregor, W.G., Trent, J.O., Miller, D.M. and Bates, P.J. (2001) Inhibition of DNA replication and induction of S phase cell cycle arrest by G-rich oligonucleotides. J. Biol. Chem. 276, 43221–43230
- Yaari-Stark, S., Nevo-Caspi, Y., Jacob-Hirsch, J., Rechavi, G., Nagler, A. and Kloog, Y. (2011) Combining the Ras inhibitor salirasib and proteasome inhibitors: a potential treatment for multiple myeloma. J. Cancer Sci. Ther 3, 187–194
10.4172/1948-5956.1000086 Google Scholar
- Yamamoto, Y. and Gaynor, R.B. (2001) Therapeutic potential of inhibition of the NF-kappaB pathway in the treatment of inflammation and cancer. J. Clin. Invest. 107, 135–142
- Yang, S., Wang, X., Contino, G., Liesa, M., Sahin, E., Ying, H., Bause, A., Li, Y., Stommel, J.M., Dell'antonio, G., Mautner, J., Tonon, G., Haigis, M., Shirihai, O.S., Doglioni, C., Bardeesy, N. and Kimmelman, A.C. (2011) Pancreatic cancers require autophagy for tumor growth. Genes Dev 25, 717–729
- Zhang, X., Lu, J., Huang, Y., Zhao, W., Chen, Y., Li, J., Gao, X., Venkataramanan, R., Sun, M., Stolz, D.B., Zhang, L. and Li, S. (2013) PEG-farnesylthiosalicylate conjugate as a nanomicellar carrier for delivery of paclitaxel. Bioconjug. Chem. 24, 464–472
