Related Experiment Video
Updated: Feb 19, 2026
Ultrasound-Guided Orthotopic Implantation of Murine Pancreatic Ductal Adenocarcinoma
Published on: November 19, 2019
MEK inhibitor-based genomically matched combinatorial targeted therapies in metastatic pancreatic adenocarcinoma with
Elizabeth D Auckley1, Stephanie Yohay1, Grace Ying2
1Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, United States.
Introduction:
Pancreatic ductal adenocarcinoma (PDAC) is often caused by mutations in multiple genes, including KRAS (activating the Ras-Raf-MEK-ERK pathway). This study evaluated the role of MEK inhibitor (MEKi)-based combinatorial targeted therapies in patients with PDAC.
Methods:
This is a retrospective/prospective observational, single-institution study, including 29 patients with metastatic PDAC with KRAS alterations, treated with MEKi therapies between 2022 and 2024.
Results:
Ten patients had KRAS G12R (34.5%), ten G12D (34.5%), and nine G12V (31%). The majority of patients received MEKi therapy as third-line and beyond (KRAS G12R/G12D/G12V: 60%/50%/78%, respectively). Median overall survival from MEKi initiation for KRAS G12R/G12D/G12V was 8.2/5.1/4.7 months (P = .5), respectively, and median progression-free survival was 4.4/2.3/1.4 months (P = .11). Six (21%) patients discontinued at least one drug in the treatment combination due to toxicity.
Conclusions:
MEKi-based combinatorial therapies had modest disease control in patients with KRAS G12R, and minimal disease control in patients with KRAS G12D/V in the late-line setting.
Insights
MEK inhibitor (MEKi) combinations showed modest disease control for KRAS G12R pancreatic cancer but limited benefit for G12D/V mutations in late-line treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Pancreatic Ductal Adenocarcinoma (PDAC) is frequently driven by KRAS mutations.
- Targeting the Ras-Raf-MEK-ERK pathway with MEK inhibitors (MEKi) is a therapeutic strategy.
- Combinatorial targeted therapies are being explored for PDAC treatment.
Purpose of the Study:
- To evaluate the efficacy of MEK inhibitor (MEKi)-based combinatorial targeted therapies.
- To assess outcomes in patients with metastatic PDAC harboring KRAS alterations.
- To analyze treatment response across different KRAS mutation subtypes (G12R, G12D, G12V).
Main Methods:
- Retrospective/prospective observational study.
- Inclusion of 29 patients with metastatic PDAC and KRAS alterations.
- Treatment with MEKi-based combinatorial therapies between 2022-2024.
Main Results:
- Patients had KRAS G12R (34.5%), G12D (34.5%), or G12V (31%) mutations.
- Most patients received MEKi therapy in third-line or later settings.
- Median overall survival: 8.2 months (G12R), 5.1 months (G12D), 4.7 months (G12V). Median progression-free survival: 4.4 months (G12R), 2.3 months (G12D), 1.4 months (G12V).
- Toxicity led to treatment discontinuation in 21% of patients.
Conclusions:
- MEKi-based combinations demonstrated modest disease control in KRAS G12R PDAC.
- Minimal disease control was observed in KRAS G12D/V PDAC patients in late-line settings.
- Toxicity is a consideration in these combinatorial regimens.
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...