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Study of Selumetinib (AZD6244)(ARRY-142886) in Combination With Irinotecan in Previously Treated Patients With Colorec

ABSTRACT: The purpose of this study is to determine whether treatment with Selumetinib (AZD6244) (Hyd-Sulfate) in combination with Irinotecan as a second treatment in patients with K-ras or B-raf mutation will prevent tumor progression and prolong progression free survival.

DISEASE(S): Colorectal Cancer,Colorectal Neoplasms

PROVIDER: 2088566 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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A Study to Assess the Safety, Tolerability and Anti-tumour Activity of Ascending Doses of Selumetinib in Combination With MEDI4736 and Selumetinib in Combination With MEDI4736 and Tremelimumab in Patients With Advanced Solid Tumours

Project description:This is a Phase I, open-label, multi-centre, drug combination study of double and triple combination oral selumetinib (AZD6244 Hyd-sulfate) plus intravenous (IV) MEDI4736 and oral selumetinib plus IV MEDI4736 and IV tremelimumab in patients with advanced solid tumours.

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Gene expression profiling during treatment of HT29 cells with selumetinib

Project description:Here, we investigate gene expression response of the BRAFV600E mutant cell line COLO205 to the MEK inhibitor selumetinib / AZD6244 / ARRY-142886. Although selumetinib causes long term G1 arrest, we observe cells stochastically entering the cell cycle without re-activation of ERK and initiation of a normal proliferative gene expression programme. Genes encoding DNA replication and repair factors are downregulated during G1 arrest, but many of these are transiently induced when cells escaping arrest enter S and G2. Nonetheless, mRNAs encoding key DNA replication factors including the MCM replicative helicase complex, PCNA and TIPIN remain at very low abundance.

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Gene expression profiling during treatment of COLO205 cells with selumetinib

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Project description:Selumetinib

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A phosphoproteomic comparison of B-RAFV600E and MKK1/2 inhibitors in melanoma cells, part 2

Project description:. To provide insight into the molecular nature of clinical responses to B-RAF(V600E) and MKK1/2 inhibition, we used quantitative mass spectrometry to characterize the inhibitor-dependent phosphoproteome of human melanoma cells treated with the B-RAF(V600E) inhibitor PLX4032 (vemurafenib) and the MKK1/2 inhibitor AZD6244 (selumetinib).. In three replicate experiments, we quantified a total of 23,986 phosphosites on 4,722 proteins. This included 1,317 phosphosites that reproducibly decreased in response to at least one inhibitor.

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Gene copy number variation profiling by microarray

Project description:Here, we investigate focal amplification patterns in and around the BRAF locus in BRAFV600Emutant COLO205 cells that acquire resistance to the MEK inhibitor Sleumetinib / AZD6244 / ARRY-142886. We find that BRAF amplifications occur frequently in COLO205 cells during acquisition of selumetinib resistance and that BRAFamplifications pre-exist selumetinib treatment but occurs predominantly via de novo mutations

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Selumetinib in adults with NF1 and inoperable plexiform neurofibroma

Project description:The MEK inhibitor selumetinib induces objective responses and provides clinical benefit in children with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PNs). To evaluate whether similar outcomes were possible in adult patients, in whom PN growth is generally slower than in pediatric patients, an open-label phase 2 study of selumetinib in adults with NF1 PNs was conducted. Correlative analysis included extraction of RNA followed by sequencing. Samples include paired specimens collected before and on treatment.

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Project description:Copy number analysis to compare parental colorectal cancer cell lines and their selumetinib-resistant derivatives and identify gene copy changes that might contribute to resistance

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RNA sequencing analysis of selumetinib-resistant CRC cells lines

Project description:RNA sequencing analysis to compare parental colorectal cancer cell lines and their selumetinib-resistant derivatives and identify expression changes and/or mutations that might contribute to resistance

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Changes in mRNA Expression by schedule-dependent combination of 5-FU and selumetinib

Project description:Anti-tumor effect of the combination between 5-FU and selumetinib was treatment schedule-dependent in BRAF or KRAS mutant CRC cells. Treatment of 5-FU for 2 days followed by selumetinib for another 2 days exhibited synergism for cell viability, whereas single or reversely combined treatment showed antagonism Microarray analysis revealed the distinct groups of genes underlying the efficacy for schedule-dependent treatment.

2020-12-30 | GSE89531 | GEO

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