OPTIM SIGNED
Optimized drug combinations for effective cancer treatment: a personalised approach.
Total Cost €
0EC-Contrib. €
0Partnership
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0OPTIM project word cloud
Explore the words cloud of the OPTIM project. It provides you a very rough idea of what is the project "OPTIM" about.
Project "OPTIM" data sheet
The following table provides information about the project.
| Coordinator |
UNIVERSITE DE GENEVE
Organization address contact info |
| Coordinator Country | Switzerland [CH] |
| Project website | https://epgl.unige.ch/mol-pharmacology/88_OPTIM_en.html |
| Total cost | 1˙199˙436 € |
| EC max contribution | 1˙199˙436 € (100%) |
| Programme |
1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC)) |
| Code Call | ERC-2015-STG |
| Funding Scheme | ERC-STG |
| Starting year | 2016 |
| Duration (year-month-day) | from 2016-05-01 to 2020-04-30 |
Partnership
Take a look of project's partnership.
| # | ||||
|---|---|---|---|---|
| 1 | UNIVERSITE DE GENEVE | CH (GENEVE) | coordinator | 1˙199˙436.00 |
Map
Project objective
This project aims to improve the treatment of metastasized colorectal carcinoma (mCRC), as treatment options after first line chemotherapy are desperately needed. The key to improvement of cancer therapy resides in optimal combination of drugs. Optimally combining drugs is non-trivial due to the large number of possibilities, especially when more than two drugs are combined at various doses. In the current research program I propose to use a differential evolution guided stochastic search algorithm to guide the way in finding optimal combination therapies. In previous research I have applied this feedback system control (FSC) technique to navigate through the enormous parametric space of nine angiostatic drugs at four doses. The straightforward iterative approach of in vitro cell viability testing and algorithm-based analysis identified optimal synergistic low-dose drug combinations. In vivo translation by maintaining the drug dose ratio led to effective anti-cancer activity, without evidence of side-effects. A new screen for optimal targeted combination treatment of advanced CRC will be performed. A series of 7 genetically different human CRC cell lines will be used in this screen, thus simulating personalized treatment. The optimized combinations will be ‘ratiometrically’ translated into orthotopic and metastasizing preclinical CRC mouse models and tested in parallel to standard chemotherapy regimens. Development of a method for a personalized screen using freshly isolated tumor cells will prepare the technology for application in the clinic. Using an innovative strategy I previously identified a series of novel markers of the tumor endothelium. After validation of these targets, this project aims for the design of new drugs to be used in a screen for optimal combination therapy for mCRC. The translational and multidisciplinary nature of the current proposal aims for preparing an improved therapeutic combination regimen for testing in cancer patients.
Publications
| year | authors and title | journal | last update |
|---|---|---|---|
| 2017 |
Judy R. van Beijnum, Patrycja Nowak-Sliwinska, Maaike van Berkel, Tse J. Wong, Arjan W. Griffioen A genomic screen for angiosuppressor genes in the tumor endothelium identifies a multifaceted angiostatic role for bromodomain containing 7 (BRD7) published pages: 641-654, ISSN: 0969-6970, DOI: 10.1007/s10456-017-9576-3 |
Angiogenesis 20/4 | 2019-06-19 |
| 2017 |
Andrea Weiss, Patrycja Nowak-Sliwinska Current Trends in Multidrug Optimization: An Alley of Future Successful Treatment of Complex Disorders published pages: 254-275, ISSN: 2472-6303, DOI: 10.1177/2472630316682338 |
SLAS TECHNOLOGY: Translating Life Sciences Innovation 22/3 | 2019-06-19 |
| 2018 |
Patrycja Nowak-Sliwinska, Kari Alitalo, Elizabeth Allen, Andrey Anisimov, Alfred C. Aplin, Robert Auerbach, Hellmut G. Augustin, David O. Bates, Judy R. van Beijnum, R. Hugh F. Bender, Gabriele Bergers, Andreas Bikfalvi, Joyce Bischoff, Barbara C. Böck, Peter C. Brooks, Federico Bussolino, Bertan Cakir, Peter Carmeliet, Daniel Castranova, Anca M. Cimpean, Ondine Cleaver, George Coukos, George E. Davis, Michele De Palma, Anna Dimberg, Ruud P. M. Dings, Valentin Djonov, Andrew C. Dudley, Neil P. Dufton, Sarah-Maria Fendt, Napoleone Ferrara, Marcus Fruttiger, Dai Fukumura, Bart Ghesquière, Yan Gong, Robert J. Griffin, Adrian L. Harris, Christopher C. W. Hughes, Nan W. Hultgren, M. Luisa Iruela-Arispe, Melita Irving, Rakesh K. Jain, Raghu Kalluri, Joanna Kalucka, Robert S. Kerbel, Jan Kitajewski, Ingeborg Klaassen, Hynda K. Kleinmann, Pieter Koolwijk, Elisabeth Kuczynski, Brenda R. Kwak, Koen Marien, Juan M. Melero-Martin, Lance L. Munn, Roberto F. Nicosia, Agnes Noel, Jussi Nurro, Anna-Karin Olsson, Tatiana V. Petrova, Kristian Pietras, Roberto Pili, Jeffrey W. Pollard, Mark J. Post, Paul H. A. Quax, Gabriel A. Rabinovich, Marius Raica, Anna M. Randi, Domenico Ribatti, Curzio Ruegg, Reinier O. Schlingemann, Stefan Schulte-Merker, Lois E. H. Smith, Jonathan W. Song, Steven A. Stacker, Jimmy Stalin, Amber N. Stratman, Maureen Van de Velde, Victor W. M. van Hinsbergh, Peter B. Vermeulen, Johannes Waltenberger, Brant M. Weinstein, Hong Xin, Bahar Yetkin-Arik, Seppo Yla-Herttuala, Mervin C. Yoder, Arjan W. Griffioen Consensus guidelines for the use and interpretation of angiogenesis assays published pages: , ISSN: 0969-6970, DOI: 10.1007/s10456-018-9613-x |
Angiogenesis | 2019-06-19 |
| 2019 |
Marloes Zoetemelk, Magdalena Rausch, Didier J. Colin, Olivier Dormond, Patrycja Nowak-Sliwinska Short-term 3D culture systems of various complexity for treatment optimization of colorectal carcinoma published pages: , ISSN: 2045-2322, DOI: 10.1038/s41598-019-42836-0 |
Scientific Reports 9/1 | 2019-08-05 |
| 2019 |
Patrycja Nowak-Sliwinska, Leonardo Scapozza, Ariel Ruiz i Altaba Drug repurposing in oncology: Compounds, pathways, phenotypes and computational approaches for colorectal cancer published pages: 434-454, ISSN: 0304-419X, DOI: 10.1016/j.bbcan.2019.04.005 |
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer 1871/2 | 2019-08-05 |
| 2017 |
Patrycja Nowak-Sliwinska, Arjan W. Griffioen Angiogenesis inhibitors in combinatorial approaches published pages: 183-184, ISSN: 0969-6970, DOI: 10.1007/s10456-017-9544-y |
Angiogenesis 20/2 | 2019-06-19 |
| 2019 |
Patrycja Nowak-Sliwinska, Judy R. van Beijnum, Elisabeth J. M. Huijbers, Paula C. Gasull, Laurie Mans, Axel Bex, Arjan W. Griffioen Oncofoetal insulin receptor isoform A marks the tumour endothelium; an underestimated pathway during tumour angiogenesis and angiostatic treatment published pages: 218-228, ISSN: 0007-0920, DOI: 10.1038/s41416-018-0347-8 |
British Journal of Cancer 120/2 | 2019-08-05 |
| 2017 |
Robert H. Berndsen, Andrea Weiss, U. Kulsoom Abdul, Tse J. Wong, Patrick Meraldi, Arjan W. Griffioen, Paul J. Dyson, Patrycja Nowak-Sliwinska Combination of ruthenium(II)-arene complex [Ru(η6-p-cymene)Cl2(pta)] (RAPTA-C) and the epidermal growth factor receptor inhibitor erlotinib results in efficient angiostatic and antitumor activity published pages: , ISSN: 2045-2322, DOI: 10.1038/srep43005 |
Scientific Reports 7/1 | 2019-08-05 |
| 2019 |
Patrycja Nowak-Sliwinska Optimization for multidrug combinations: Challenges and perspectives in complex disorders published pages: , ISSN: 1043-6618, DOI: 10.1016/j.phrs.2019.02.004 |
Pharmacological Research | 2019-06-27 |
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