Lung cancer is the leading cause of cancer mortality worldwide and recently the oncologists are coincident about the necessity to identify new more effective molecules able to fight this cancer entity. Due to the fact that pH deregulation is a common feature that confers adaptive advantages to cancers, we presume that molecules that selectively decrease the intracellular pH would be of great interest as new chemotherapeutic agents for lung cancer treatment. Tambjamines are natural marine compounds with anion transporter properties that showed an interesting in vitro apoptotic effects against cancer cells. This project aims to identify novel potent and specific anticancer anion transporter compounds chemically related to tambjamines, characterize in deep their cytostatic and/or cytotoxic effects, elucidate the major changes in signaling pathways components caused by their treatment and identifying their molecular target. Moreover, we aim to evaluate drug safety and efficacy of these compounds in vivo, to develop an innovative drug nanoformulation in order to improve selectivity and efficacy as well as a promising drug administration route. Finally, translational research in human lung primary cultures and patient-derived xenograft models will be conducted.
Using the combined expertise of three different groups in medicinal chemistry, novel drug formulation, computational modeling, in vitro cell biology and biochemistry techniques, transcriptomic and proteomic analysis, as well as translational research by xenograft models we will be able to complete the preclinical trials of a promising new family of compounds.