Optimized low-dose combinatorial drug treatment boosts selectivity and efficacy of colorectal carcinoma treatment.

ABSTRACT: The current standard of care for colorectal cancer (CRC) is a combination of chemotherapeutics, often supplemented with targeted biological drugs. An urgent need exists for improved drug efficacy and minimized side effects, especially at late-stage disease. We employed the phenotypically driven therapeutically guided multidrug optimization (TGMO) technology to identify optimized drug combinations (ODCs) in CRC. We identified low-dose synergistic and selective ODCs for a panel of six human CRC cell lines also active in heterotypic 3D co-culture models. Transcriptome sequencing and phosphoproteome analyses showed that the mechanisms of action of these ODCs converged toward MAP kinase signaling and cell cycle inhibition. Two cell-specific ODCs were translated to in vivo mouse models. The ODCs

SUBMITTER: Zoetemelk M 

PROVIDER: S-EPMC7607171 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature