biostudies-literatureUnknown130(5)Contreras-Toledo D<h4>Introduction</h4>The mitogen-activated protein kinase (MAPK) signalling network aberrations in metastatic colorectal cancer (mCRC) generate intrinsic dynamic effects and temporal variations that are crucial but often overlooked in clinical trial populations. Here, we investigate the time-varying impact of MAPK pathway mutation genotype on each treatment line's contribution to the overall clinical course.<h4>Methods</h4>The PROMETEO study focused on mCRC patients undergoing second-line treatment at 20 hospitals. We evaluated genotypes and employed flexible models to analyse the dynamic effect of each mutation.<h4>Results</h4>We examined data derived from 1160 patients. The effects of KRAS G12C or G12V, and BRAF V600E are clearly time-varying, with unexpected consequences such as the delBritish journal of cancer777-787https://www.ebi.ac.uk/biostudies/studies/S-EPMC10912758biostudies-literatureDynamic nature of BRAF or KRAS p.G12C mutations in second-line therapy for advanced colorectal cancer patients: do early and late effects exist?PMC10912758Vazquez Rivera FVirgili Manrique ACAlonso VFernandez-Diaz ABCovela Rua MMartin Carnicero AAlonso BMontes AFGonzalez Villaroel PAparicio JSalva FJimenez-Fonseca PJimeno Mate RCameselle Garcia SAsensio Martinez EGuillot MCarmona-Bayonas AAlcaide JMelian Sosa MCousillas Castineiras AGonzalez Astorga BLopez CLCastanon Lopez CContreras-Toledo DLopez Munoz AMfalseDynamic nature of BRAF or KRAS p.G12C mutations in second-line therapy for advanced colorectal cancer patients: do early and late effects exist?<h4>Introduction</h4>The mitogen-activated protein kinase (MAPK) signalling network aberrations in metastatic colorectal cancer (mCRC) generate intrinsic dynamic effects and temporal variations that are crucial but often overlooked in clinical trial populations. Here, we investigate the time-varying impact of MAPK pathway mutation genotype on each treatment line's contribution to the overall clinical course.<h4>Methods</h4>The PROMETEO study focused on mCRC patients undergoing second-line treatment at 20 hospitals. We evaluated genotypes and employed flexible models to analyse the dynamic effect of each mutation.<h4>Results</h4>We examined data derived from 1160 patients. The effects of KRAS G12C or G12V, and BRAF V600E are clearly time-varying, with unexpected consequences such as the del2024-01-01T00:00:00Z2024 Mar2026-06-02T07:08:29.036Z2025-04-04T21:49:40.973ZS-EPMC109127583819160910.1038/s41416-023-02563-w