A drug library screen identifies Carbenoxolone as novel FOXO inhibitor that overcomes FOXO3-mediated chemoprotection in high-stage neuroblastoma.

The transcription factor FOXO3 has been associated in different tumor entities with hallmarks of cancer, including metastasis, tumor angiogenesis, maintenance of tumor-initiating stem cells, and drug resistance. In neuroblastoma (NB), we recently demonstrated that nuclear FOXO3 promotes tumor angiogenesis in vivo and chemoresistance in vitro. Hence, inhibiting the transcriptional activity of FOXO3 is a promising therapeutic strategy.

Treatment According to a Comprehensive Molecular Profiling Can Lead to a Better Outcome in Heavily Pretreated Patients With Metastatic Cancer: Data of a Pooled Analysis.

Purpose: Improvements in systemic treatment have led to a prolongation of survival and quality of life in patients with metastatic tumors in recent years. However, despite this improved standard of care, it is expected that the progression-free survival (PFS) for patients with refractory cancers will continue to decline over subsequent therapy lines. In those patients, studies and meta-analyses showed that treatment based on multiplatform molecular profiling (MMP) of tumor tissue may derive a clinical benefit.

Innovation in oncology clinical trial design.

Progress in and better understanding of cancer biology causes a shift in cancer drug development: away from the evaluation of drugs in large tumour histology defined patient populations towards targeted agents in increasingly heterogeneous molecularly defined subpopulations. This requires novel approaches in clinical trial design by academia and industry, and development of new assessment tools by regulatory authorities. Pharmaceutical industry is developing new targeted agents generating many clinical studies, including target combinations.

3D-cultivation of NSCLC cell lines induce gene expression alterations of key cancer-associated pathways and mimic conditions.

This work evaluated gene expression differences between a hanging-drop 3D NSCLC model and 2D cell cultures and their relevance by comparison to patient-derived data from The Cancer Genome Atlas. Gene expression of 2D and 3D cultures for Colo699 and A549 were assessed using Affymetrix HuGene 1.0 ST gene chips.