Inhibition of JAK/STAT3 signalling pathway in cancer therapy

JAK/STAT3 signaling pathway plays a crucial role in oncogenesis and the development of cellular senescence. Its inhibition is considered to be a promising way of controlling cancer progression and suppressing the adverse effects of senescent cells on the tissue microenvironment. Currently, there is a lack of specific STAT3 inhibitors with potential clinical use. The goal of the project is to prepare and validate new druggable inhibitors of STAT3 which will be able to inhibit tumor growth and the development of cellular senescence and to evaluate the efficacy of the current and novel STAT3 inhibitors in inhibiting tumor growth and its acceleration by senescent cells. Furthermore, the project focuses on the modification of an immunophenotype and secretome of senescent cells utilizing both in vitro cultures of cancer cells and murine tumor models.
The overall goal is to develop a combination of chemo- and immuno-therapy and a therapeutic scheme in which STAT3 inhibitors would eliminate the adverse effects of the genotoxic/senescence-inducing anti-tumor therapy, which is also connected with preventing the development of the residual tumor disease and with increasing the effectiveness of the subsequent immunotherapy.

The main researcher of the project
MUDr. Zdeněk Hodný CSc.
E-mail Zdenek.Hodny@img.cas.cz
Insitution: Institute of Molecular Genetics of the AS CR, v.v.i.