The Immunotherapy Revolution by Jason R. Williams

Author:Jason R. Williams
Language: eng
Format: epub
Publisher: Gatekeeper Press
Published: 2019-02-15T00:00:00+00:00

MEK inhibitors

In 2016 results were presented at the European Society for Medical Oncology (ESMO) by Johanna Bendell, MD on a phase 1 study combining atezolizumab (PD-L1 inhibitor) with cobimetinib (MEK inhibitor) for patients with microsatellite stable (MSS) metastatic colorectal cancer. In general, MSS patients do not respond as well to immunotherapy and unfortunately make up the majority of patients (95%). This combination offers the hope that MSS metastatic colorectal patients may have an improved chance to respond to one of the most widely used type of immunotherapy, PD-1/PD-L1 inhibitors. The results were pretty modest, with 17% partial response, 22% stable disease, with a response duration from 4 months to greater than 15 months. The exact mechanism still seems to not be well understood, but most likely involves a decrease in immune suppressive mediators such as COX-2 and Arg1 with increasing cytotoxic T cell infiltration in the tumor microenvironment. Ebert el al published a study in Immunity, 2016 that MEK inhibition reduces CD8+ T cell apoptosis during chronic T cell receptor stimulation. Often when the immune system is chronically activated, like in cancer, the immune cells that attack the cancer can be fatigued and may die off. This indicates a MEK inhibitor may assist in preventing this immune suppression from developing. Certainly in patients who have MSS colorectal cancer and are considering systemic immunotherapy with a PD-1/PD-L1 inhibitor, this combination with a MEK inhibitor should be an option.

Download

Copyright Disclaimer:
This site does not store any files on its server. We only index and link to content provided by other sites. Please contact the content providers to delete copyright contents if any and email us, we'll remove relevant links or contents immediately.