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OPTIM SIGNED

Optimized drug combinations for effective cancer treatment: a personalised approach.

Total Cost €

0

EC-Contrib. €

0

Partnership

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 Outcomes and results

 OPTIM 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.

innovative    translated    fsc    viability    translation    angiostatic    cell    therapy    space    navigate    vitro    metastasizing    evolution    iterative    translational    personalized    dose    treatment    combination    maintaining    preclinical    search    screen    optimized    guided    mcrc    drugs    therapies    tested    freshly    parametric    line    led    optimal    prepare    models    ratiometrically    chemotherapy    ratio    endothelium    carcinoma    markers    metastasized    therapeutic    synergistic    differential    genetically    lines    optimally    possibilities    tumor    doses    human    algorithm    cancer    first    technique    colorectal    parallel    nature    simulating    desperately    enormous    previously    combinations    vivo    strategy    stochastic    resides    crc    preparing    combined    patients    feedback    clinic    options    regimens    improvement    anti    nine    isolated    cells    guide    standard    regimen    mouse    trivial    drug    orthotopic    multidisciplinary    validation    straightforward    performed    series    combining   

Project "OPTIM" data sheet

The following table provides information about the project.

Coordinator		 UNIVERSITE DE GENEVE 

Organization address
address: RUE DU GENERAL DUFOUR 24
city: GENEVE
postcode: 1211
website: www.unige.ch

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.
 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.

# participants  country  role  EC contrib. [€] 
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
List of publications.
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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