Host – Tumor Interactions during Cancer Therapy – Dr. Yuval Shaked’s Lab @Technion
Reporter: Aviva Lev-Ari, PhD, RN
Yuval Shaked, PhD
Assistant Professor of Molecular Pharmacology |
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PhD, 2004 – Hebrew University, Israel |
Figure Legend:
Anti-cancer therapy affects both the host and the tumor. Host cells or factors home to the treated tumor microenvironment and promote tumor growth and even spread of metastasis. Blocking such therapy-induced tumor effects can improve treatment outcome.
Understanding host – tumor interactions during cancer therapy
Personalized medicine holds promise of better cures with fewer side effects for many diseases. Individualized cancer therapy is sometimes utilized after multiple attempts of standard therapies and is based on several considerations, such as tumor type, acquired resistance to a specific therapy, previous treatment protocols, and other tumor-related factors. We have recently demonstrated that many cancer therapies can induce pro-tumorigenic or metastatic effects that derive not only from the tumor cells themselves, but also from host cells within the tumor microenvironment. The focus of research in my laboratory is to identify, characterize, and seek ways to block such pro-tumorigenic host effects observed after anti-cancer therapy, and thus potentially improve the outcome of current cancer therapies. Our findings may foster a paradigm shift in cancer therapy by minimizing the gap between preclinical findings and the clinical setting, laying the foundation for development of entirely new strategies for improving cancer therapy.
Representative publications
Benayoun L, Gingis-Velitski S, Voloshin T, Segal E, Segev R, Munster M, Bril R, Satchi-Fainaro R, Scherer SJ, Shaked Y. 2012. Tumor initiating cells of various tumor types exhibit differential angiogenic properties and react differently to antiangiogenic drugs. Stem Cells 30, 1831-41.
Gingis-Velitski S, Loven D, Benayoun L, Munster M, Bril R, Voloshin T, Alishekevitz D, Bertolini F, Shaked Y. 2011. Host response to short-term, single-agent chemotherapy induces matrix metalloproteinase-9 expression and accelerates metastasis in mice. Cancer Research 71, 6986-96.
Voloshin T, Gingis-Veltski S, Milsom C, Man S, Munster M, Kerbel RS, Shaked Y. 2011. G-CSF supplementation with chemotherapy can promote revascularization and subsequent tumor regrowth: prevention by a CXCR4 antagonist. Blood 118, 3426-35.
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Tumor-derived microparticles induce bone marrow-derived cell mobilization and tumor homing: A process regulated by osteopontin
2013 Yuval Shaked, PhD
Authors : Fremder E, Munster M, Aharon A, Miller V, Gingis-Velitski S, Voloshin T, Alishekevitz D, Bril R, Scherer SJ, Loven D, Brenner B, Shaked Y. Int J Cancer. 2013 Dec 18. doi:10.1002/ijc.28678. [Epub ahead of print] PubMed PMID: 24347266.
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Low-dose metronomic chemotherapy: from past experience to new paradigms in the treatment of cancer
2013 Yuval Shaked, PhD
Authors : Loven D, Hasnis E, Bertolini F, Shaked Y. Drug Discov Today. 2013 Feb;18(3-4):193-201.
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Differential therapeutic effects of anti-VEGF-A antibody in different tumor models: implications for choosing appropriate tumor models for drug testing.
2013 Yuval Shaked, PhD
Authors : Alishekevitz D, Bril R, Loven D, Miller V, Voloshin T, Gingis-Velitski S, Fremder E, Scherer SJ, Shaked Y. Mol Cancer Ther. 2013 Oct 22. [Epub ahead of print] PubMed PMID: 24150126.
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Poly(ethylene glycol)-paclitaxel-alendronate self-assembled micelles for the targeted treatment of breast cancer bone metastases
2013 Yuval Shaked, PhD
Authors : Miller K, Clementi C, Polyak D, Eldar-Boock A, Benayoun L, Barshack I, Shaked Y, Pasut G, Satchi-Fainaro R. Biomaterials. 2013 May;34(15):3795-806.
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In vitro enrichment of tumor-initiating cells from human established cell lines.
2013 Yuval Shaked, PhD
Authors : Benayoun L, Shaked Y. Curr Protoc Stem Cell Biol. 2013 Feb;Chapter 3:Unit 3.7. doi: 10.1002/9780470151808.sc0307s24. PubMed PMID: 23404675.
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Tumor initiating cells of various tumor types exhibit differential angiogenic properties and react differently to antiangiogenic drugs
2012 Yuval Shaked, PhD
Authors : Benayoun L, Gingis-Velitski S, Voloshin T, Segal E, Segev R, Munster M, Bril R, Satchi-Fainaro R, Scherer SJ, Shaked Y. Stem Cells 30, 1831-41.
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Host Response to Short-term, Single-Agent Chemotherapy Induces Matrix Metalloproteinase-9 Expression and Accelerates Metastasis in Mice.
2011 Yuval Shaked, PhD
Authors : Gingis-Velitski S, Loven D, Benayoun L, Munster M, Bril R, Voloshin T, Cancer Res. 2011 Nov 15;71(22):6986-96.
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G-CSF supplementation with chemotherapy can promote revascularization and subsequent tumor regrowth: prevention by a CXCR4 antagonist.
2011 Yuval Shaked, PhD
Authors : Voloshin T, Gingis-Velitski S, Bril R, Benayoun L, Munster M, Milsom C, Man S, Blood. 2011 Jun 17. 118(12):3426-35.
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Antiangiogenic Antitumor Activity of HPMA Copolymer-Paclitaxel-Alendronate Conjugate on Breast Cancer Bone Metastasis Mouse Model.
2011 Yuval Shaked, PhD
Authors : Miller K, Eldar-Boock A, Polyak D, Segal E, Benayoun L, Shaked Y, Satchi-Fainaro R. Mol Pharm. 2011 May 17. [Epub ahead of print]
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Enhanced anti-tumor activity and safety profile of targeted nano-scaled HPMA copolymer-alendronate-TNP-470 conjugate in the treatment of bone malignances.
2011 Yuval Shaked, PhD
Authors : Kopeckova P, Shaked Y, Kopecek J, Satchi-Fainaro Biomaterials. 2011 Mar 21. 32(19):4450-63.
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The angiogenic profile of colorectal cancer patients following open or laparoscopic colectomy.
2010 Yuval Shaked, PhD
Authors : Voloshin T, Gingis-Velitski S, Shaked Y. Cancer Biol Ther. 2010 Nov 10;10(7):686-8.
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Predictive Potential of Angiogenic Growth Factors and Circulating Endothelial Cells in Breast Cancer Patients Receiving Metronomic Chemotherapy Plus Bevacizumab
2009 Yuval Shaked, PhD
Authors : Calleri A, Bono A, Bagnardi V, Quarna J, Mancuso P, Rabascio C, Dellapasqua S, Campagnoli E, Shaked Y, Goldhirsch A, Colleoni M, Bertolini F. Clin Cancer Res. 2009 Dec 15;15(24):7652-7657
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Contribution of granulocyte colony-stimulating factor to the acute mobilization of endothelial precursor cells by vascular disrupting agents
2009 Yuval Shaked, PhD
Authors : Shaked Y, Tang T, Woloszynek J, Daenen LG, Man S, Xu P, Cai SR, Arbeit JM, Voest EE, Chaplin DJ, Smythe J, Harris A, Nathan P, Judson I, Rustin G, Bertolini F, Link DC, Kerbel RS. Cancer Res. 2009 69:7524-8.
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Bone marrow derived cells in tumor angiogenesis and growth: are they the good, the bad or the evil?
2009 Yuval Shaked, PhD
Authors : Shaked Y, Voest EE. Biochim Biophys Acta. 2009 1796(1):1-4.
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Rapid chemotherapy-induced acute endothelial progenitor cell mobilization: implications for antiangiogenic drugs as chemosensitizing agents
2008 Yuval Shaked, PhD
Authors : Shaked, Y., Henke, E., Roodhart, J. M. L., Mancuso, P., Langenberg, M. H. G., Colleoni, M., Daenen, L. G., Man, S., Xu, P., Emmenegger, U., Tang, T., Zhu, Z., Witte, L., Streiter, R. M., Bertolini, F., Voest, E. E., Benezra, R., Kerbel, R. S. Cancer Cell 14, 263-273.
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Antiangiogenic strategies on defense: on the possibility of blocking rebounds by the tumor vasculature after chemotherapy
2007 Yuval Shaked, PhD
Authors : Shaked, Y., Kerbel, R. S. Cancer Res 67, 7055-7058.
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Therapy-induced acute recruitment of circulating endothelial progenitor cells to tumors
2006 Yuval Shaked, PhD
Authors : Shaked, Y., Ciarrocchi, A., Franco, M., Lee, C. R., Man, S., Cheung, A. M., Hicklin, D. J., Chaplin, D., Foster, F. S., Benezra, R., Kerbel, R. S. Science 313, 1785-1787.
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