# Utilizing MEK Inhibition to Sensitize Microsatellite Stable Colorectal Cancer to Immune Checkpoint Therapy

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2020 · $548,097

## Abstract

PROJECT SUMMARY/ABSTRACT
The purpose of this proposal is to determine the efficacy of the combination of targeted therapy against
MEK and VEGF in combination with immunotherapy in patients with refractory, metastatic colorectal
cancer. The development of immunotherapy targeting immune regulatory checkpoints has started a new
era in the treatment of cancer. Blockade of these immune checkpoints has shown tumor regression in
several tumor types, however in colorectal cancer patients activity has been restricted to patients that have
high microsatellite instability (MSI). However, a phase Ib study combining a MEK inhibitor,
cobimetinib, and a PDL-1 inhibitor, atezolizumab, in patients with microsatellite stable metastatic
colorectal cancer patients demonstrated a combination effect which provides support for combination
strategies for these patients that are MSS
Biopsies obtained from this trial will be used for two specific purposes; 1) evaluate immune and pathway
modulation in patients with microsatellite stable metastatic colorectal cancer, and 2) the development of
humanized patient-derived xenografts to conduct a co-preclinical trial.
Our group, in collaboration with the immunology team at the University of Colorado Anschutz Medical
Campus, has developed a humanized patient derived xenograft mouse model. In preliminary studies with
this model we have observed anti-tumor activity in colorectal cancer models that are MSI-high
demonstrating that the model has the potential to mimic what is seen in the clinical setting and to allow
for preclinical studies of immune checkpoint inhibition.
These data support our overall hypothesis that humanized colorectal PDX models can be utilized to
evaluate combination strategies with immunotherapy and other targeted agents in MSS patients. We
propose to 1) Identify immune and pathway modulation following treatment with binimetinib,
bevacizumab, and pembrolizumab. 2) Determine the efficacy of the combination of binimetinib,
bevacizumab, and immune checkpoint inhibitors in humanized patient derived xenograft models of
microsatellite stable colorectal cancer, and 3) Identify immune and pathway modulation in humanized
patient derived xenograft models treated with the combination.

## Key facts

- **NIH application ID:** 10007595
- **Project number:** 5R01CA229259-03
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Christopher Hanyoung Lieu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $548,097
- **Award type:** 5
- **Project period:** 2018-09-24 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10007595

## Citation

> US National Institutes of Health, RePORTER application 10007595, Utilizing MEK Inhibition to Sensitize Microsatellite Stable Colorectal Cancer to Immune Checkpoint Therapy (5R01CA229259-03). Retrieved via AI Analytics 2026-06-14 from https://api.ai-analytics.org/grant/nih/10007595. Licensed CC0.

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