Ionizing radiation (IR) remains one of the most effective tools in cancer therapy. It combines the properties of an extremely efficient cellular damaging agent with a high degree of spatial specificity. Approximately 50% of all cancer patients receive radiation therapy at some point in their treatment. The major biological determinant of radiotherapy failure is tumor radioresistance. The molecular mechanisms underlying tumor radioresistance, which can potentially be used as targets for tumor radiosensitization, are currently far from being clear.
The primary goal of our lab is to identify and better understand some of the molecular pathways that, when aberrantly activated, may lead to tumor radioresistance. In this respect, our main focus is the relation between deregulated receptor tyrosine kinase (RTK) signaling pathways, and in particular, those associated with the hepatocyte growth factor receptor/C-Met, and resistance to IR-induced cytotoxicity. Aberrant RTK activation due to overexpression, autocrine/paracrine mechanisms, gene rearrangements and point mutations is a known hallmark of numerous human malignancies and has recently been suggested to interfere with tumor response to chemo/radiotherapy. Our specific research interests in this regard are –
- Understanding the molecular pathways triggered by RTKs that may eventually lead to cellular IR-resistance.
- Correlation between genetic alterations of various RTK signaling components and clinical outcome post radiotherapy.
- Studying various molecular and pharmacological means interfering with RTK signaling in order to modulate the radio/chemotherapy response of tumors.