Professional title: Associate Professor in General Pathology
Date of primary qualification: 1997
Current institution:
University of Palermo, Department of Surgical and Oncological Sciences, Cellular and Molecular Pathophysiology Laboratory
Title of invited presentation:
Colon cancer stem cells: Clinical and therapeutic implications
Learning objectives:
The involvement of CSCs in several types of tumors is gaining interest. The CSC hypothesis has important implications for understanding key biological processes of carcinogenesis and developing innovative therapeutic strategies selectively targeted to the population that fuels neoplastic growth and maintenance. Antineoplastic agents have been largely developed through testing in animal models as well as in phase II human trials. In both of these, the measured outcome has been shrinkage of tumors. However, if CSCs are inherently resistant to therapeutic agents and if these cells comprise only a minority of the tumor cell population, then shrinkage of tumors may reflect the effects of these agents on the differentiated cells of a tumor rather than on the CSC compartment. This may explain why in clinical trials for advanced cancers, tumor regression often does not translate into clinically significant increases in patient survival. This has been shown in many tumor types, including breast and colon tumors. Besides, the understanding and the evaluation of the mechanisms that regulate the apoptotic process and consequently cancer stem cells proliferation, would be useful for the elaboration of new and more appropriate therapies, that together with conventional chemotherapeutic drugs, could reduce cancer stem cells survival, which seem to be the most responsible cells for the tumoral minimal residual disease induction and metastasis formation.
Summary of research background
In the last years, Giorgio Stassi became a pioneer in isolating and characterizing human cancer stem cells from solid tumors and in elucidating their remarkable apoptosis resistance mediated by interleukins. He has identified the role of certain cytokines, most importantly of IL-4, to block apoptosis in cancer cells in an autocrine fashion, i.e. the tumor cell itself provides the apoptosis-inhibitory stimulus by production of IL-4. They also described the importance of the neutralization of IL-4 in the sensitization of cancer cells and cancer stem cells to conventional chemotherapy. Recently, he is focusing on the role of microenvironment on cancer stem cells. He aims to identify a molecular marker of a metastatic behaviour that could be clinically exploited both as a biomarker and therapeutic target in the adjuvant setting.His principal research focus are: tumor sensitization by neutralizing IL-4, regulation of apoptosis by IL-4, characterization and sensitization to chemotherapy of colon and breast cancer stem cells, tumorigenic and metastatic properties of cancer stem cells, evaluation of molecular targets involved in the survival and differentiation pathways of cancer stem cells in vitro and in vivo.
Relevant peer reviewed publications within last 5 years
- Charafe-Jauffret E, Ginestier C, Iovino F, Wicinski J, Cervera N, Finetti P, Hur MH, Diebel ME, Monville F, Dutcher J, Brown M, Viens P, Xerri L, Bertucci F, Stassi G., Dontu G, Birnbaum D, Wicha MS. Breast Cancer Cell Lines Contain Functional Cancer Stem Cells with Metastatic Capacity and a Distinct Molecular Signature. Cancer Res. 2009 Feb 3.
- Francipane M. G., Eterno V., Spina V., Bini M., Scerrino G., Buscemi G., Gulotta G., Todaro M., Dieli F., De Maria R. and Stassi G. SOCS3 sensitizes anaplastic thyroid cancer to standard chemotherapy. Cancer Res. 2009 Aug 1; 69(15):6141-8.
- Charafe-Jauffret E, Ginestier C, Iovino F, Tarpin C, Diebel M, Esterni B, Houvenaeghel G, Extra JM, Bertucci F, Jacquemier J, Xerri L, Dontu G, Stassi G., Xiao Y, Barsky SH, Birnbaum D, Viens P, Wicha MS. Aldehyde Dehydrogenase 1-Positive Cancer Stem Cells Mediate Metastasis and Poor Clinical Outcome in Inflammatory Breast Cancer. Clin Cancer Res. 2010 Jan 1;16(1):45-55.
- Kemper K, Sprick MR, de Bree M, Scopelliti A, Vermeulen L, Hoek M, Zeilstra J, Pals ST, Mehmet H, Stassi G., Medema JP. The AC133 epitope, but not the CD133 protein, is lost upon cancer stem cell differentiation. Cancer Res. 2010 Jan 15;70(2):719-29.
- Cammareri P., Scopelliti A., Todaro M., Eterno V., Francescangeli F., Pat Moyer M., Agrusa A., Dieli F., Zeuner A., Stassi G. Aurora-A is essential for the tumorigenic capacity and chemoresistance of colorectal cancer stem cells. Cancer Res. 2010 Jun 1; 70(11) 4655-65
- Vermeulen L., De Sousa Melo F., van der Heijden M., Borovski T., de Jong J. H., Rodermond H., Tuynman J. B., Sprick M. R., Kemper K., Richel D. J., Stassi G. and Medema J. P.. Wnt Activity Defines Colon Cancer Stem Cells and is Regulated by the Microenvironment. Nature Cell Biology 2010 May; 12(5): 468-76
- Lombardo Y, Scopelliti A, Cammareri P, Todaro M, Iovino F, Ricci-Vitiani L, Gulotta G, Dieli F, De Maria R, Stassi G. BMP4 induces differentiation of colorectal cancer stem cells and increases their response to chemotherapy in mice. Gastroenterology. 2010 Oct 14
- Todaro M, Iovino F, Eterno V, Cammareri P, Gambara G, Espina V, Gulotta G, Dieli F, Giordano S, De Maria R, Stassi G. Tumorigenic and Metastatic Activity of Human Thyroid Cancer Stem Cells. Cancer Res. 2010 Oct 19.
- Ricci-Vitiani L, Pallini R, Biffoni M, Todaro M, Invernici G, Cenci T, Maira G, Parati EA, Stassi G, Larocca LM, De Maria R. Tumour vascularization via endothelial differentiation of glioblastoma stem-like cells. Nature. 2010 Dec 9;468(7325):824-8.
- Caccamo N, La Mendola C, Orlando V, Meraviglia S, Todaro M, Stassi G, Sireci G, Fournié JJ, Dieli F. Differentiation, phenotype, and function of interleukin-17-producing human V{gamma}9V{delta}2 T cells. Blood. 2011 Jul 7;118(1):129-38.
- M. Todaro, M. G. Francipane, J. P. Medema, and G. Stassi. Colon cancer stem cells: promise of targeted therapy. Gastroenterology 2010 Jun; 138(6):2151-2162.
- Valent P, Bonnet D, De Maria R, Lapidot T, Copland M, Melo JV, Chomienne C, Ishikawa F, Schuringa JJ, Stassi G, Huntly B, Herrmann H, Soulier J, Roesch A, Schuurhuis GJ, Wöhrer S, Arock M, Zuber J, Cerny-Reiterer S, Johnsen HE, Andreeff M, Eaves C. Cancer stem cell definitions and terminology: the devil is in the details. Nat Rev Cancer. 2012 Nov;12(11):767-75.
