Christos Sotiriou, MD, PhD

2007-2008 BCRF Project:
Dr. Sotiriou and his colleagues previously identified 62 genes that can predict which women have a high risk of breast cancer recurrence when treated with tamoxifen (manuscript submitted for publication). Recently, also using gene expression profiling, they defined a genomic grade that identified two subgroups of ER-positive breast tumors associated with a distinct clinical outcome, both in untreated and tamoxifen-treated breast cancer patients.

This work was recently published in Journal of Clinical Oncology. Advances in new technologies such as microarray analysis, together with the human genome sequencing, has led to a considerable increase in our understanding of breast cancer biology and has also greatly improved their classification. Gene expression profiling studies have demonstrated that breast tumors could be divided in at least 4 different subgroups with different biological characteristics and clinical outcomes. MicroRNAs (miRNA) are small non-coding RNAs that can negatively regulate gene expression. It has recently been shown that miRNAs can contribute to the development of cancer. The study of their expression profiles might thus represent a powerful tool that can be used for human cancer molecular classification, prognosis, but more importantly for the prediction of response to therapeutic treatments.

The aim of Dr. Sotiriou's project is to analyze the expression profiles of miRNAs in order to improve breast cancer molecular classification for estrogen receptor-positive tumors, and endocrine therapy response prediction to optimize cancer treatment and possibly lead to the identification of new therapeutic drugs.

Mid-Year Progress Report:
Dr. Sotiriou and his team have identified a "genomic" tumor grade (GGI), which reflects differentiation and tumor progression on the basis of gene expression profiles and which was effectively associated with disease outcome in breast cancer far beyond the currently used clinico-pathological parameters. They further demonstrated that this genomic grade was able to identify two clinically distinct subgroups within the breast cancer tumors diagnosed as positive for the presence of the estrogen-receptor (ER). The majority of these patients are currently treated with adjuvant tamoxifen. However, up to 40% of these patients will develop incurable tumor recurrence.

In this project, the researchers aim to improve the selection of the patients who will benefit from this treatment in order to increase the cure rates from breast cancer. In the first part of the project, the researchers investigate the potential value of the GGI for predicting outcome in tamoxifen-treated patients and letrozole-treated patients in a multicentric prospective trial. They have already converted the GGI into a simple and accurate RT-PCR test, which can potentially be used as a routine clinical diagnostic assay, improving the prognosis of the ER-positive tumors and also the prediction of the patient response to tamoxifen treatment. Finally, they aim to analyze the expression profiles of microRNAs (miRNAs) in order to improve breast cancer molecular classification for the ER-positive tumors and endocrine therapy response prediction, and to possibly lead to the identification of new therapeutic drugs.

The researchers demonstrated that their expression profiling might provide complementary information regarding the molecular classification of breast cancer. They also identified several miRNAs as potential candidates for clinical outcome and for response to tamoxifen in ER-positive breast cancer patients.

Bio:
Dr. Christos Sotiriou earned a medical degree from the Universit� Libre de Bruxelles, Belgium, in 1993. He did his internal medicine/oncology residency at the Jules Bordet Institute (Profs. J. Klastersky, M. Piccart), and he earned his specialty in internal medicine and medical oncology in July 1999 at the Universit� Libre de Bruxelles. During his last year of residency, he worked as research fellow at the Laboratory of Endocrinology, Bone Metabolism and Breast Oncology (Dr J. Body), at the Jules Bordet Institute, supported by an educational grant from the Belgian National Foundation of Scientific Research.

From October 1999 till September 2001, he worked as basic research fellow, at the Division of Clinical Sciences, Microarray Facility, National Cancer Institute (Pr Edison Liu), National Institutes of Health, Bethesda, MD, USA, supported by an educational grant from the Association "Yvonne et Thomas Rucquois - Les Amis de l'Institut Jules Bordet - Belgium", and the National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. During his fellowship he received a Scholar in Training Award for the study of the expression profiling analysis of von Hippel-Lindau tumor suppressor gene from the American Association for Cancer Research, March 24-28, 2001, New Orleans, USA. Since October 2001, he has been Assistant Professor at the Medical Oncology Clinic of the Jules Bordet Institute.

Dr. Sotiriou earned his doctor of philosophy degree (PhD) from the Université Libre de Bruxelles, Belgium in September 2004. He was promoted Head of the Functional Genomics and Translational Research Unit of the Jules Bordet Institute in October 2004 and, in October 2005 he will become a research associate at the Belgian National Foundation of Scientific Research (FNRS). Dr. Sotiriou's research focuses on genomics and molecular biology in breast cancer.

Dr. Sotiriou is a member of ASCO, AACR, and ESMO and also member of the Steering and Executive committee of TRANSBIG, a "sister" network of the Breast International Group (BIG aisbl), dedicated multinational translational research linked to prospective clinical trials, since 2003. He presently has several publications in peer review journals and three book chapters. He is also a reviewer for several scientific journals. He received several educational and research grants from the Swiss Foundation MEDIC, the National Foundation of Cancer Research, the Université Libre de Bruxelles, the "Fonds Jean-Claude Heuson", the Fondation Lambeau-Marteau, the Belgian Federation against Cancer, and the European Union Framework VI Programme.