Open AccessOptimized low‐dose combinatorial drug treatment boosts selectivity and efficacy of colorectal carcinoma treatment
Author(s) -
Zoetemelk Marloes,
Ramzy George M.,
Rausch Magdalena,
Koessler Thibaud,
Beijnum Judy R.,
Weiss Andrea,
Mieville Valentin,
Piersma Sander R.,
Haas Richard R.,
DelucingeVivier Céline,
Andres Axel,
Toso Christian,
Henneman Alexander A.,
Ragusa Simone,
Petrova Tatiana V.,
Docquier Mylène,
McKee Thomas A.,
Jimenez Connie R.,
Daali Youssef,
Griffioen Arjan W.,
RubbiaBrandt Laura,
Dietrich PierreYves,
NowakSliwinska Patrycja
Publication year - 2020
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.12797
Subject(s) - folfox , drug , colorectal cancer , in vivo , pharmacology , cancer research , chemotherapy , cancer , medicine , biology , oxaliplatin , microbiology and biotechnology
Therapeutically guided multidrug optimization (TGMO) technology, composed of experimental testing and in silico modelling, allowed identification of synergistic and selective low‐dose optimized drug combinations (ODCs) active in multiple colorectal carcinoma models. The mechanisms of action of the ODCs was established using transcriptome sequencing and phosphoproteomic analyses. Our results indicate that simultaneous multitarget inhibition of important deregulated pathways has strong therapeutic potential and translational value between tumor types.