Zoetemelk, Marloes; Ramzy, George M.; Rausch, Magdalena; Koessler, Thibaud; van Beijnum, Judy R.; Weiss, Andrea; Mieville, Valentin; Piersma, Sander R.; de Haas, Richard R.; Delucinge-Vivier, Celine; Andres, Axel; Toso, Christian; Henneman, Alexander A.; Ragusa, Simone; Petrova, Tatiana V.; Docquier, Mylene; McKee, Thomas A.; Jimenez, Connie R.; Daali, Youssef; Griffioen, Arjan W.; Rubbia-Brandt, Laura; Dietrich, Pierre-Yves; Nowak-Sliwinska, Patrycja published the artcile< Optimized low-dose combinatorial drug treatment boosts selectivity and efficacy of colorectal carcinoma treatment>, Safety of Calcium folinate, the main research area is colorectal carcinoma drug treatment optimized low dose combinatorial; colorectal carcinoma; combination treatment; drug-drug interactions; drug-target interactions; phosphoproteomics; synergy.
The current standard of care for colorectal cancer (CRC) is a combination of chemotherapeutics, often supplemented with targeted biol. 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) technol. 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 reduced tumor growth by ∼80%, outperforming standard chemotherapy (FOLFOX). No toxicity was observed for the ODCs, while significant side effects were induced in the group treated with FOLFOX therapy. Identified ODCs demonstrated significantly enhanced bioavailability of the individual components. Finally, ODCs were also active in primary cells from CRC patient tumor tissues. Taken together, we show that the TGMO technol. efficiently identifies selective and potent low-dose drug combinations, optimized regardless of tumor mutation status, outperforming conventional chemotherapy.
Molecular Oncology published new progress about Animal gene, c-kit Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 1492-18-8 belongs to class alcohols-buliding-blocks, and the molecular formula is C20H21CaN7O7, Safety of Calcium folinate.
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