WYE-125132 / Pfizer - LARVOL DELTA

Discovering novel ALK-lung carcinoma therapeutic strategies by identifying combinations with Alectinib from ALK-positive lung carcinoma cell lines (AACR 2024) - "Cells were characterized by bulk-RNAseq, bulk-DNA seq, Reverse-phase protein array, and Mass spectrometry to identify perturbed RNA pathways, DNA mutations, and proteome alterations. In this study, we present for the first time, a group of compounds, such as Gilteritinib, Trametinib, Dinaciclib, WYE-125132, Cenisertib, SN-38 which exhibit the capacity to induce cytotoxic effects in ALK-positive lung cancer cells, when combined with Alectinib. Through the integration of different multiomic approaches on five ALK-positive lung cancer cell lines, we have pinpointed a novel role of MAPK, CDK, and mTOR, pathways and their regulators, as a promising avenue for advancing treatment strategies for ALK-positive lung cancer. These findings, along with the identification of several other significant targetable elements illustrate a new approach towards the discovery of new drug combinations and targetable pathways to tackle ALK TKI resistance in ALK-positive patients before it..."

Preclinical • Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • KRAS • STAT3

mTOR Promotes Tissue Factor Expression and Activity in EGFR-Mutant Cancer. (PubMed, Front Oncol) - "Application of mTORC1/2 inhibitors (AZD8055, WYE-125132, MTI-31, and rapamycin) or genetic mTORC-depletion all reduced TF expression, which appeared to be differentially mediated depending on cellular context. Thus, our results have identified TF as a functional biomarker of mTOR. Downregulation of mTOR-TF axis activity likely contributes to the therapeutic mechanism of mTORC1/2- and TF-targeted agents in EGFR-mut advanced NSCLC and GBM."

Journal • Cardiovascular • Fibrosis • Glioblastoma • Hematological Disorders • Hemophilia • Immunology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • Thrombosis • CD31 • EGFR • mTOR