Medical University of Vienna
Institute for Cancer Research
Department of Medicine I
Borschkegasse 8a
1090 Vienna, Austria
Phone: +43 1 40160-57594
Fax: +43 1 40160-957502
E-Mail: petra.heffeter@meduniwien.ac.at
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Chemotherapy and therapy with small targeted molecules are two major strategies for therapy of human cancer at the disseminated stage. During the last decades, thousands of compounds have been developed and consequently have improved therapy effectiveness. However, even when using new targeted therapeutics, such therapy is often limited by strong side effects, resistance development and insufficient tumor accumulation.
We focus on the development of several new strategies to overcome these limitations:
Advertised project “Novel albumin-binding oxaliplatin prodrugs to circumvent resistance”
Enhanced accumulation of albumin in tumors has been successfully exploited to increase the efficacy of paclitaxel (Abraxane) and doxorubicin (Aldoxorubicin). Recently, we have synthesized the first albumin-targeting prodrugs of platinum drugs, which are currently under development to undergo phase I clinical trials, following the demonstration of outstanding in vitro and in vivo anticancer activity. Based on these preliminary data we hypothesize that albumin-bound prodrugs can overcome resistance and thus increase efficacy of platinum drugs. Our laboratory has established a wide range of in vitro and in vivo models to study intrinsic and acquired resistance mechanisms. This unique resource, consisting of more than 20 platinum-resistant cell models (many of them tumorigenic in mice), will serve as a screening platform to investigate the potential of our new drug delivery system to overcome drug resistance mechanisms, which usually hamper the efficacy of platinum drugs. In parallel, new in vitro and vivo models (cell lines, grafts, organoids) with acquired resistance to the albumin-targeting prodrugs will be established and analyzed for the underlying resistance mechanisms. The functional relevance of the most prominent resistance mechanisms will be verified by CRISPR/Cas9 based genome editing. Finally, the anticancer activity, intratumoral accumulation and pharmacokinetics of the novel albumin-binding prodrugs will be evaluated in in vivo resistance models, focusing also on alterations in albumin homeostasis.
Selected publications
My master’s internship has been performed in the “translational cancer therapy research” area, so to continue my study in the same area, I chose to participate at the IPPTO program. My project is to focus on Preclinical evaluation of novel albumin-binding pro-drugs and resistance circumvention.