Targeting autophagy for anti-cancer therapy
- Reference number
- ID16-0034
- Start and end dates
- 170101-211231
- Amount granted
- 2 500 000 SEK
- Administrative organization
- Karolinska Institutet
- Research area
- Life Sciences
Summary
The main objective of this pre-clinical research is to characterize novel drugs – inhibitors of a lipid Vps34 kinase (Vps34-Is), involved in autophagy and endosomal trafficking, and to assess their activity in anti-cancer treatment in a pre-clinical setting. This involves the following aims: (1) a detailed characterization of the activity of Vps34-Is in human cancer models using mouse xenografts; (2) pinpointing anti-cancer treatments where combination therapy with Vps34-Is will enhance anti-cancer effects and allow overcoming drug resistance. (3) identification of biomarkers predictive for treatment response and for monitoring autophagy in cancer patients This project brings together the competence of drug discovery of Sprint Bioscience who have screened, developed and optimized novel Vps34-Is, and the expertise of an academic basic and translational research of D. Grandér’s group who are studying the mechanisms of autophagy induction by anti-cancer drugs. The PhD study based on this multidisciplinary project between industry and academia will address critical issues of drug discovery, such as mechanistic understanding of the target protein and of the predictive biomarkers for anti-cancer treatment and combination therapy. Such a complex and balanced approach will lead to a faster implementation of these novel drugs into an individualized clinical practice.
Popular science description
Developing new medicines to treat diseases is a complex and difficult task, and most of the drug discovery programs fail before reaching the clinic and the patients. Deep understanding about the biological processes behind the disease, and having good tools to measure efficacy of the new drug during the stages of development of the drug will improve the chances of success, since compounds can be continuously optimized to have the desired properties. The more one knows about the target, the disease and the interplay existing between these two, the better compounds one can develop. We want to improve knowledge about a validated target for cancer treatment and develop biomarkers that will; i) facilitate the evaluation of the drugs when tested, ii) be used to select patients that would benefit from our drug and iii) measure if they are responding to the treatment. Altogether, better understanding of the disease and a new approach to treat cancer.