Local invasion and metastasis are the deadliest characteristics of cancer, as they account for the majority of cancer associated deaths. However, the wide range of invasive phenotypes, and the ability of cancer cells to switch among them, has prevailed the development of antimetastatic therapies. Recently, we have established the concept of migrastatics as drugs targeted against common features of invasion modes, stressing the requirement to evaluate drugs based on anti-invasive, rather than anti-proliferative, properties.
The aim of the proposed project would be to investigate novel migrastatic candidates identified based on a large screen of TGF beta inhibitors analogues. The most promising compound shown to inhibit cancer cell invasion in our pilot screen was further modified in order to enhance its migrastatic properties. The ability of the novel compounds to inhibit cancer cell invasion will be extensively studied by the applicant both in vitro and in vivo, together with the molecular mechanisms underlying their migrastatic properties.
The work of the applicant will concentrate on three main aims: i) to analyze the anti-invasive effects of novel TGF beta inhibitors analogs in vitro, ii) to elucidate the molecular mechanisms, through which the anti-invasive effects of compounds are exerted, iii) to analyze the effect of selected compounds on experimental tumors and metastasizing in vivo.
The proposal will lead to the development of novel anti-invasive and anti-metastatic compounds with considerable potential for the translation into the clinics.
Funding and project approval:
CENTRE FOR TUMOUR ECOLOGY
Research of the Cancer Microenvironment Supporting Cancer Growth and Spread
Reg. No. CZ.02.1.01/0.0/0.0/16_019/0000785
Required application materials:
How to submit application materials:
Please send email with the required application materials to Assoc. Prof. Jan Brábek:
email@example.com, Faculty of Science, Charles University, Prague.
The application deadline is July 23, 2021.
For more information please visit the webpage of the JUNIOR Fund project of the Charles University.