The treatment of patients with bronchioalveolar carcinoma (BAC) is far from optimal and new strategies to improve the survival of these patients are needed.  One way to increase the chance of response in BAC patients is to understand the mechanisms behind the uncontrolled growth of cancer cells.  In adenocarcinomas, one of those mechanisms has been studies in details, leading to the successful approval of drugs inhibiting this mechanism.

This mechanism is called “angiogenesis”, such as the formation of new blood vessels that bring “food” to the growing tumors. The role of angiogenesis in BACs remains to be investigated.  One of the key proteins driving the growth of new blood vessels in tumors is the vascular endothelial growth factor receptor 2 (VEGFR-2). In this application, we aim to study the biology of VEGFR-2 to see how the activity and level of this protein varies in different BACs. More importantly, we will evaluate whether there is a genetic basis for the differences in VEGFR-2 levels observed in patients with BACs.

We have previously discovered that the VEGFR-2 gene is highly variable in the general population, and we hypothesize that these genetic variations might affect the level and function of VEGFR-2 in BACs. For testing these hypotheses, we will evaluate the effect of the variation in VEGFR-2 gene on the expression of the VEGFR-2 protein in BACs. We will also test their effect on the amount of angiogenesis in these tumors. In addition, we will use cell line models in vitro to further establish the role of the VEGFR-2 gene variants at a cellular level.

The ultimate aim of this proposal is to use this information to improve the cure of BAC patients by identifying those patients that might benefit from angiogenesis inhibitors according to their genetic make up of the VEGFR-2 gene.