The main interest of our Laboratory is the study of molecular events underlying the oncogenic process, especially in colorectal cancer. Colorectal cancer is the second leading cause of cancer related dead in the western world. In 2004 colorectal cancer accounted for approximately 13% of all cancer cases and cancer-related deaths in the European Union, with over 375,000 new cases and more than 200,000 deaths due to this disease. Understanding of the molecular mechanisms underlying the tumorigenic process is a key step that will allow the identification of new markers of prognosis, response to therapy and therapeutic targets. These in turn will lead to an improvement of the survival and quality of life of a large number of patients with colorectal cancer.

Dr. Arango graduated in Biological Sciences in 1994 at Universidad Autonoma de Madrid (Spain) and obtained his PhD in 1998 at the University College Dublin (UCD) in Ireland where he became familiar with the anatomy and physiology of the intestine, and studied different ways of manipulating the cell cycle of intestinal stem cells in an attempt to minimize the effects of radiotherapy in the abdominal and pelvic region. From 1999 to 2003, Dr. Arango was a Postdoctoral Fellow and an Instructor at the Albert Einstein Cancer Center in New York, where he gained extensive knowledge on the different genomic approaches to understand the differences between normal and tumor tissue as well as between tumors from patients with good and bad prognosis or response to treatment. Dr. Arango moved in 2003 to the Center of Excellence in Disease Genetics at Biomedicum Helsinki (Finland) as a Visiting Scientist, where he began different lines of independent research. In 2005, Dr. Arango became the Leader of the Molecular Oncology Group at the CIBBIM-Nanomedicine at the Vall d’Hebron Hospital in Barcelona.

These are currently the main lines of research at the Molecular Oncology Group:

1. Identification of new markers of prognosis and response to treatment for colorectal cancer patients.
   Colorectal cancer is the second leading cause of cancer related dead in the western world and represents a serious health concern. In 2004 colorectal cancer accounted for approximately 13% of all cancer cases and cancer-relateddeaths in the European Union, with 376,000 new cases and 204,000 deaths due to this disease. To put in perspective the magnitude of health the problem posed by colorectal cancer it is important to highlight that approximately one in 17 EU citizens will develop malignant tumors in their colon or rectum in the course of their life. Patients diagnosed with early stage (I and II) tumors have good prognosis (5-year survival greater than 80%). However, the majority of patients have advanced disease (stage III or IV) at the moment of their initial diagnosis and the 5-year survival rates for these patients ranges from 40% to less than 5%. There is, therefore, great need to improve the treatment of these patients.
   We use high throughput techniques to find new markers that when used alone or in combination with other makers, they can be used to discriminate between patients that have high and low probability of recurrence after treatment. We then follow up these experiments using in vitro and in vivo experiments to investigate the functional relevance of these new markers for colorectal cancer initiation and progression.

   

   Figure 1: EPHB4 expression and survival of colorectal cancer

2. Role of EPH signaling in cancer.
   EPH receptors are the largest family of receptor tyrosine kinases (RTKs), proteins that play a crucial role in many biological processes such as embryonic development, cell proliferation and differentiation. EPH signaling plays an important role in the regulation of proliferation and cell migration in the intestinal epithelium. Defects in EPH signaling have been reported in multiple tumor types and at least EPHB2 and EPHB4 have been shown to be important tumor suppressor genes in colorectal cancer. Our group is currently investigating the role of several additional members of the EPH family in gastrointestinal tumorigenesis.

   

   Figure 2: Effects of EPHB4 on intestinal proliferation.

3. Role of small GTPases in colorectal cancer.
   RhoA is a member of the small GTPase family that regulates cytoskeletal remodeling, protein and lipid trafficking, transcriptional activation and cell growth. We have recently demonstrated that patients whose tumors have low levels of RhoA have significantly worse prognosis than patients with high RhoA tumor levels (Arango et al., 2005).
   We are studying the molecular mechanism underlying our previous observation showing that low RhoA levels are associated with poor prognosis of colorectal cancer patients. For this purpose, we are using in vitro isogenic systems as well as animal studies and analysis of achieved materials from human tumor samples.

   

   Figure 3. Subcellular localization of MYO1A.