Germline variation in the insulin-like growth factor pathway and risk of Barrett's esophagus and esophageal adenocarcinoma
Contains fulltext : 235640.pdf (Publisher’s version ) (Closed access) Genome-wide association studies (GWAS) of esophageal adenocarcinoma (EAC) and its precursor, Barrett's esophagus (BE), have uncovered significant genetic components of risk, but most heritability remains unexplained. Targeted assessment of genetic variation in biologically relevant pathways using novel analytical approaches may identify missed susceptibility signals. Central obesity, a key BE/EAC risk factor, is linked to systemic inflammation, altered hormonal signaling and insulin-like growth factor (IGF) axis dysfunction. Here, we assessed IGF-related genetic variation and risk of BE and EAC. Principal component analys…
PD-0024 Phase I/II Study of Folfiri Plus the MEK1/2 Inhibitor Pimasertib (MSC1936369B) as Second-Line Treatment for KRAS Mutated Metastatic Colorectal Cancer
ABSTRACT Introduction Pimasertib is a highly selective inhibitor of the MEK1/2 kinases of the MAPK pathway. It demonstrates potent antitumor activity in cell lines and xenograft models with activating (mainly BRAF and KRAS) mutations. A two-part study, comprising a safety run-in part followed by a randomized phase II part, was designed to investigate FOLFIRI plus pimasertib as second-line treatment for patients with KRAS mutated (mt) metastatic colorectal cancer (mCRC). The results of the safety run-in part, conducted primarily to determine the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D), are reported here. Methods Patients with KRAS mt mCRC progressing on first-li…