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TRP CHANNELS-FUNCTIONALIZED NANOPARTICLES TO TARGET PROSTATE CANCER VASCULARIZATION

 

Prostate cancer (PCa) is the most common non-cutaneous human malignancy and the second most lethal tumor among men, with the highest incidence in industrialized countries. PCa is highly angiogenic: extensive studies have revealed that angiogenesis plays an essential role in its development, invasion, and metastasis. Microvessel density has been shown to be a prognostic marker. Although the results of anti-angiogenic therapy in preclinical models of prostate cancer provided promising results, some discrepancy between these data and those obtained in clinical trials were observed suggesting that the discovery of new therapeutic targets is therefore necessary to give a new input to the antiangiogenic therapy.

Being involved in nearly all of the ‘hallmarks of cancer’, there is an increasing consensus on the idea that ion channels play a significant role in driving cancer progression at all stages. Accumulating evidence tends to demonstrate that the development of some cancers could also involve such ion channel aberrations and, therefore, could be classified as channelopathies. Therefore ion channels may be seen as potential novel therapeutic, diagnostic, and prognostic targets for anti-cancer therapies.

On the other hand one of the main properties of the channels is their wide distribution within the differnt organs. Selective targeting of its components in cancer cells  and vessels remains the major challenge for therapeutic use, as pharmacological impairment of any of these components would likely produce significant toxicity to normal cells. This problem could be overcome by directed targeted therapies taking advantage from nano-biomedicine.

The general objective of this project is to establish the role of TRP channels regulating Ca2+ signature of tumor angiogenesis regulating PCa progression and metastasis and to develop new nanoparticles functionalized with TRP channels activators or inhibitors as targets for the diagnosis and treatment of advanced PCa

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