Projects

The Research projects ongoing in Dr. Dréau's laboratory focus on understanding the molecular, cellular, tissular and physiological bases of metastases associated with cancers of epithelial origin.

• The cancers of epithelial origin include: the most lethal skin cancer, i.e. melanoma and the most common solid tumor in female i.e., breast cancer. In these cancers as in others, the occurrence of metastases is associated with a high mortality (see the site of the American Cancer Society for details on cancer statistics in the US: http://www.cancer.org ).

• The development of metastases is a multi-step process, which, from the tumor standpoint, includes:
- Development of tumor cells with metastatic potentials.
- Detachment, migration of tumor cells generally through the vascular system (blood, lymph vessels), and anchoring within the host tissue.
- Growth of the metastatic mass requiring the concurrent development of vessels, i.e. neo-angiogenesis, which provide oxygen and various nutriments.
- Preventing responses of the immune system throughout all the steps associated with the development of tumor metastases.

Dr. Dréau's research center on the mechanisms of cancer metastasis, and the vascular and immune interactions associated with cancer growth. More specifically, the following aspects of cancer metastasis are studied:

• Key features of Metastatic Tumors:

What are the mechanisms implicated in the differentiation of a metastatic tumor cell from non-metastatic tumor cells? What is the combination of parameters/features associated with a rapid development of metastases?
In the laboratory this research is conducted on melanoma cell lines. The identification of key features associated with the development of metastases involves many molecular and cellular technologies and the use of in vivo models. In addition, in vivo models contribute to the analysis.
The results of these studies may allow a more efficient diagnostic and treatment of patients with solid tumors including melanoma patients.

• Anchoring and Growth of Metastatic Tumors:

Although some of the protein associated in the detachment, migration and anchoring within an organ with tissular specificity different from the tumor cell origin have been defined; the mechanism and the molecules associated with the development of distant metastases have not. Moreover, epidemiological data suggests that metastases occur in different organ based on the tumor origin. Also understanding the effect of tumor growth within an organ is also crucial.
In the laboratory this research is conducted on a breast cancer bone metastases in vivo model. Additionally, in collaboration with Dr. Iain McKillop, the development of distant liver metastases and their effects of liver functions are analyzed.
From a diagnostic standpoint, an understanding of the minimal features associated with the development of brain or liver metastases would be of tremendous help in the clinical setting.

• Vascularization of the Metastatic Tumors:

As the tumor grows, it requires the development of new vessels, i.e., neo-angiogenesis. The new vessels transport oxygen and various nutriments to the tumor cells allowing for additional growth of the tumor mass. The ability to generate neo-angiogenesis varies greatly between tumors. These Interactions with the vascular System are critical to the development of metastases.
In the laboratory, we are interested in these interactions and how the tumor cells production of angiogenic factors including endothelin-1 (ET-1) and vascular endothelial growth factor (VEGF) stirs the development of new vessels. These studies are conducted, in collaboration with Dr. Mark  Clemens, on an in vivo breast cancer model of the development of bone metastases. This in vivo model closely mimics the development of breast cancer metastases to the bone and allows the analysis of the effect of endothelin-1, a key protein associated with the development of new vessels, a critical step for tumor growth.
The gathered information will provide a better understanding of the step associated with the generation of new vessels and may deliver the bases for the development of angiogenic-based treatments of aggressive metastatic tumors. Indeed, preventing tumor growth by preventing the development of new vessels (therefore starving the tumor cells) may become a clinical option for patients with solid tumor including breast cancer patients.

• Interactions Immune System and Metastases:

One of the reasons associated with the development of metastases is the ability of cancer cells to evade the immune system. Although the interactions immune system and tumor cells are complex, current data indicate that there is active “fight” between the defense system and the tumor mass. The mechanisms associated with the ability of tumor cells to evade the host immune system mechanisms may be active (e.g., production of cytokines affecting the immune response) and/or passive (e.g., passive selection of the tumor cell without any recognizable antigen). In some cancers, like melanoma and renal cell carcinoma, boosting the immune responses either by the administration of systemic treatments (e.g., IL-2, IFN) or more specific vaccines has shown some clinical success. However, mechanisms behind the development of an immune response resulting in the cancer cure in some cancer patients remain unknown. The laboratory in collaboration with Dr. Ian  Marriott  is interested in tumor cell expression of genes susceptible to modulate/redirect the immune response. These genes/proteins may be clear targets for the development of efficient cancer treatment.