Obiettivo
Abnormal vascular network formation is a prerequisite for tumor growth. This phenomenon has prompted the development of therapeutic approaches targeting molecules involved in the formation of pathological blood vessels such as VEGF and its receptors VEGFR1, VEGFR2 and VEGFR3. Although some patients benefited from such an approach, the majority of patients had a poor outcome through a transient decrease of the tumor/metastases accompanied by the selection of more aggressive tumors cells.
Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults, responsible for approximately 80% of cases. It has been described as being among the most lethal of all the urological cancers. One major problem encountered in cancer patients, including RCC patients treated with anti-angiogenesis drugs, is the recurrence of metastases and even the development of new metastatic niches. Therefore, we postulate that the over-expression of VEGF-C, a growth factor for vascular and lymphatic endothelial cells, is responsible for tumor cells metastasis in response to anti-angiogenesis therapy.
Hence, the objective of our project is to determine the molecular mechanisms leading to the expression of VEGF-C after treatment with anti-angiogenesis drugs. Because VEGF-C may constitute both a predictive marker and a new pertinent therapeutic target, its role in acquired metastatic properties of RCC following anti-angiogenesis treatments deserves to be rigorously investigated. We will focus on the transcriptional regulation of VEGF-C and the stability of its mRNA. These goals will be achieved through the use of relevant cellular and animal models.
Since the anti-angiogenesis therapies lead to genetic adaptation of tumor cells, probably due to expression of receptors targeted by anti-angiogenesis drugs, our ultimate goal is to identify important partners that play a key role in the escape to anti-angiogenesis therapies that should have been curative.
Campo scientifico
Argomento(i)
Invito a presentare proposte
FP7-PEOPLE-2013-IEF
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Meccanismo di finanziamento
MC-IEF - Intra-European Fellowships (IEF)Coordinatore
75794 Paris
Francia