STAT3 is constitutively active in a number of cancers, comprising a promising anticancer target. This project identified a novel, small molecule STAT3 inhibitor, VS-43, which efficiently downregulates the cellular levels of pSTAT3 in cancer cells, induces apoptosis, synergises with chemotherapy and radiation, and restores cellular sensitivity in resistant cells.
Eingereicht von: Dr. Konstantinos Kiakos
Firma/Universität: University of Vienna
The emergence of resistance not only to cytotoxic, DNA-damaging agents but also to molecular targeted drugs (EGFR, MEK inhibitors), is an acute medical problem in the management of cancer, as it limits the drugs’ clinical efficacy and deprives cancer patients of critical therapeutic interventions. The unmet need for the development of effective and innovative strategies to resensitise cancer cells and overcome chemoresistance is ever pressing.
At a time that it is evident that combination treatments of targeted agents with cytotoxic chemotherapy are necessary to overcome the activation of mechanisms of drug resistance, our undergoing work presents a novel, targeted, small molecule inhibitor, endowed with anticancer activity as a stand-alone agent, with – additionally – chemo- and radio- senisiting properties. VS-43 is of a novel chemical design, and inherently fluoresces enabling the determination of its cellular uptake. The concurrent work of elucidating the underlying molecular and cellular mechanisms for the observed sensitising effects, is essential for the formulation of rational drug combinations and the optimisation of future therapeutic strategies for the treatment of cancer patients.