Special Issue "Cardiotonic Steroids"
Deadline for manuscript submissions: closed (20 February 2017)
Prof. Dr. Robert Kiss
Laboratorie de Cancérologie et de Toxicologie Expérimentale, Faculté de Pharmacie, Université Libre de Bruxelles (ULB), Brussels, Belgium
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Interests: cancer research; natural compounds; non-apoptotic cell death; metastatis; in vivo models; multidrug resistance; glioblastoma; melanoma; cell migration; phenotypic screening
The sodium/potassium pump (the Na+/K+-ATPase, i.e., NaK), with its highly specific ligands (i.e., cardiotonic steroids including cardenolides and bufadienolides), seems a promising target for combating cancers associated with dismal prognoses, which mainly relate to the resistance of cancer cells (as metastatic ones) to pro-apoptotic cytotoxic insults and to the acquisition of the multidrug resistant (MDR) phenotype during chronic treatment. Indeed, NaK plays a key role in cell adhesion and has abnormal expression and activity that could be implicated in the development and progression of different cancers, including glioblastoma, melanoma, and non-small-cell lung cancers, among others. The activation of NaK triggers distinct signaling pathways in normal versus cancer cells, and several cardiotonic steroids have already been demonstrated to be less toxic in normal than in cancer cells. In addition, several cardiotonic steroids also kill various types of apoptosis-resistant and/or MDR cancer models. However, various challenges still exist to move cardiotonic steroids in clinical development for combating various types of cancers. One of these challenges relates to how managing the toxicity of these compounds, according to the limitations of existing preclinical models, will adequately predict the cardiotoxic potential of new molecules in man. Two other challenges relate to the potential of chemical modifications to reduce the cardiovascular side-effects and improve the anti-cancer activity of new molecules, and the development of tumor-targeting vectors to accumulate these compounds on tumor sites, while decreasing systemic toxicity
Prof. Dr. Robert Kiss
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- cardiotonic steroids
- drug targeting
- medicinal chemistry