Enhancing efficacy of the MEK inhibitor trametinib with paclitaxel in -mutated colorectal cancer.

Background: is frequently mutated in the tumors of patients with metastatic colorectal cancer (mCRC) and thus represents a valid target for therapy. However, the strategies of targeting KRAS directly and targeting the downstream effector mitogen-activated protein kinase kinase (MEK) via monotherapies have shown limited efficacy. Thus, there is a strong need for novel, effective combination therapies to improve MEK-inhibitor efficacy in patients with -mutated mCRC.

Oncogenic KRAS Mutations Confer a Unique Mechanotransduction Response to Peristalsis in Colorectal Cancer Cells.

Colorectal cancer (CRC) tumors start as polyps on the inner lining of the colorectum, where they are exposed to the mechanics of peristalsis. Our previous work leveraged a custom-built peristalsis bioreactor to demonstrate that colonic peristalsis led to cancer stem cell enrichment in CRC cells. However, this malignant mechanotransductive response was confined to select CRC lines that harbored an oncogenic mutation in the KRAS gene.

Enhancing efficacy of the MEK inhibitor trametinib with paclitaxel in -mutated colorectal cancer.

Background: is frequently mutated in the tumors of patients with metastatic colorectal cancer (mCRC) and thus represents a valid target for therapy. However, the strategies of targeting KRAS directly and targeting the downstream effector mitogen-activated protein kinase kinase (MEK) via monotherapies have shown limited efficacy. Thus, there is a strong need for novel, effective combination therapies to improve MEK-inhibitor efficacy in patients with -mutated mCRC.

Endoscopy for the diagnosis and treatment of gastrointestinal bleeding caused by malignancy.

Background And Aim: The diagnosis and treatment of gastrointestinal (GI) bleeding secondary to malignancy can be challenging. Endoscopy is the gold standard to diagnose and treat gastrointestinal bleeding but clinical characteristics and outcomes of patients with malignancy-related bleeding are not well understood. This study aims to look at clinical characteristics, endoscopic findings, safety and clinical outcomes of endoscopic interventions for GI malignancy-related bleeding.

PIK3CA mutations in plasma circulating tumor DNA predict survival and treatment outcomes in patients with advanced cancers.

Background: Oncogenic mutations in PIK3CA are prevalent in diverse cancers and can be targeted with inhibitors of the phosphoinositide-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway. Analysis of circulating tumor DNA (ctDNA) provides a minimally invasive approach to detect clinically actionable PIK3CA mutations.

Patients And Methods: We analyzed PIK3CA hotspot mutation frequency by droplet digital PCR (QX 200; BioRad) using 16 ng of unamplified plasma-derived cell-free DNA from 68 patients with advanced solid tumors (breast cancer, n = 41; colorectal cancer, n = 13; other tumor types, n = 14).