PD Dr. Alexandre Arcaro
Departement Klinische Forschung
Abteilung für Pädiatrische Hämatologie/Onkologie
University of Bern, Pathologie L619
Phone: +41 31 632 32 87
Fax: +41 31 308 80 28
Activties and Research Interests
Project title: “Identification and characterization of leukemia stem cells in pediatric acute lymphoblastic leukemia using an in vivo model”
B-cell precursor ALL (BCP-ALL) is the most common form of cancer in children. Although around 80% of children can be cured with current chemotherapy regimens, cases with high relapse risk can be defined at diagnosis, and relapsed ALL remains a leading cause of cancer deaths in childhood. Preclinical models and global assessment of gene regulation in ALL patients can speed the evaluation of rationally targeted agents and their optimal incorporation into combination chemotherapies. The cancer stem cell theory predicts that efficacy against human BCP-ALL stem cells (LSCs) is required for cure, emphasizing the need for preclinical models that measure LSCs.
Our recent published work has shown that LSCs residing within the essentially non-proliferating, immunophenotypic immature blast cell population may have a better chance of surviving an anti-proliferation-based chemotherapeutic regimen than LSCs residing within a more mature and actively proliferating blast cell population. In this project we want to further characterize the potential LSC population we have identified by in vitro studies in an in vivo model using immunodeficient mice.
Our long-term goals will be to develop new understanding and treatment of cases that cannot currently be cured, such as BCP-ALL cases at relapse, with high-risk features, or poor eventual outcomes.
- Wojtalla, A., Fischer, B., Kotelevets, N., Mauri, F.A., Sobek, J., Rehrauer, H., Wotzkow, C., Tschan, M.P., Seckl, M.J., Zangemeister-Wittke, U., and Arcaro A. (2012). Targeting the Phosphoinositide 3-Kinase p110α Isoform Impairs Cell Proliferation, Survival and Tumor Growth in Small Cell Lung Cancer. Clinical Cancer Research, DOI:10.1158/1078-0432.CCR-12-1138
- Salm, F., Cwiek, P., Ghosal, A., Buccarello, A.-L., Largey, F., Wotzkow, C., Höland, K., Styp-Rekowska, B., Djonov, V., Zlobec, I., Bodmer, N., Gross, N., Westermann, F., Schäfer, S.C., and Arcaro, A. (2012). RNA interference screening identifies a novel role for autocrine fibroblast growth factor signaling in neuroblastoma chemoresistance. Oncogene, doi:10.1038/onc.2012.416
- Wojtalla, A., Salm, F., Christiansen, D.G., Cremona,T., Cwiek, P., Shalaby, T., Gross, N., Grotzer, M.A., and Arcaro. A. (2012). Novel Agents Targeting the IGF-1R/PI3K Pathway Impair Cell Proliferation and Survival in Subsets of Medulloblastoma and Neuroblastoma. Plos One, 7(10):e47109.
- Błajecka, K., Marinov, M., Leitner, L., Uth, K., Posern, G., and Arcaro, A. (2012). Phosphoinositide 3-Kinase C2β Regulates RhoA and the Actin Cytoskeleton through an Interaction with Dbl. Plos One, 7(9):e44945
- Guerreiro, A.S., Fattet, S., Kulesza, D.W., Atamer, A., Elsing, A.N., Shalaby, T., Jackson, S.P., Schoenwaelder, S.M., Grotzer, M.A., Delattre, O., and Arcaro, A. (2011). A sensitized RNA interference screen identifies a novel role for the PI3K p110g isoform in medulloblastoma cell proliferation and chemoresistance. Mol. Cancer Res., 9, 925-935.
- Marinov, M., Ziogas, A., Pardo, O.E., Tan, L.T., Lane, H.A., Lemoine, N.R., Zangemeister-Wittke, U., Seckl, M.J., and Arcaro, A. (2009). Akt/mTOR pathway activation and Bcl-2 family proteins modulate the sensitivity of human small cell lung cancer cells to RAD001 (Everolimus). Clinical Cancer Research, 15, 1277-1287
- Guerreiro, A.S., Fattet, S., Fischer, B., Shalaby, T., Jackson, S.P., Schoenwaelder, S.M., Grotzer, M.A., Delattre, O., and Arcaro, A. (2008). Targeting the PI3K p110a isoform inhibits medulloblastoma proliferation, chemoresistance and migration. Clinical Cancer Research, 14, 6761-6769
- Boller, D., Schramm, A., Doepfner, KT., Shalaby, T., von Bueren, A.O., Eggert, A., Grotzer, M.A., and Arcaro, A. (2008). Targeting the phosphoinositide 3-kinase isoform p110d impairs growth and survival in neuroblastoma cells. Clinical Cancer Research, 14, 1172-1181
- Doepfner, K.T., Spertini, O., and Arcaro, A. (2007). Autocrine insulin-like growth factor-I signaling promotes growth and survival of human acute myeloid leukemia cells via the phosphoinositide 3-kinase/Akt pathway. Leukemia, 21, 1921–1930
- 10. Khanzada, U.K., Pardo, O.E., Meier, C., Downward, J., Seckl, M.J., and Arcaro, A. (2006). Potent inhibition of small cell lung cancer cell growth by simvastatin reveals selective functions of Ras isoforms in growth factor signalling. Oncogene, 25, 877-887