Related Experiment Video
Updated: Jun 8, 2026
Generation and Expansion of Primary, Malignant Pleural Mesothelioma Tumor Lines
Published on: April 21, 2022
Clinical implications of novel activating EGFR mutations in malignant peritoneal mesothelioma
Jason M Foster1, Uppala Radhakrishna, Venkatesh Govindarajan
1Department of Surgery, Creighton Cancer Center, Creighton University, Omaha, NE, USA. jfosterm@unmc.edu
Background:
There is a paucity of information about the molecular perturbations involved in MPM tumor formation. We previously reported that EGFR-TK mutations in MPM were predictive of achieving optimal surgical cytoreduction, but the status of EGFR pathway activation potential of these mutations was not known. Here we present the mutant EGFR activating potential and the matured survival data of the EGFR mutant(mut+) relative to wild type EGFR(mut-) mesothelioma.
Methods:
Twenty-nine patients were evaluated and their tumors were probed for mutations in the catalytic TK-domain. Twenty-five patients were treated with cytoreductive surgery and complete clinical data was available for comparison of the mut+ and mut- groups. A COS-7 cell expression model was used to determine mutation activating profiles and response to erlotinib.
Results:
Functional mutations were found in 31%(9/29) of patients; 7 of these mutations were novel and another was the L858R mutation. All missense mutations were found to be activating mutations and responsive to erlotinib. Of the 25 patients managed surgically, there were 7 mut+ and 18 mut-. Two of 7 (29%) mut+ developed progressive disease and died with a median follow-up time of 22 months; while 13/18 (72%) mut- developed progressive disease and 10/18 (56%) died with median TTP of 12 months and median survival of 14 months.
Conclusions:
The novel EGFR mutations identified are activating mutations responsive to erlotinib. The mut+ subset have a 'relative' improved outcome. Erlotinib may have a role in MPM and exploration for mutations in a larger patient cohort is warranted.
Insights
New EGFR mutations in malignant pleural mesothelioma (MPM) are activating and respond to erlotinib. Patients with these EGFR mutations showed improved survival outcomes compared to those without, suggesting erlotinib
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Limited understanding of molecular alterations in malignant pleural mesothelioma (MPM).
- Previous findings linked EGFR-TK mutations to optimal surgical cytoreduction in MPM.
- The activating potential of these EGFR mutations and their impact on patient survival were previously unknown.
Purpose of the Study:
- To investigate the activating potential of EGFR mutations in MPM.
- To compare survival outcomes between EGFR mutant-positive (mut+) and EGFR wild-type (mut-) MPM patients.
- To assess the response of mutant EGFR in MPM to erlotinib.
Main Methods:
- Genomic analysis of the EGFR catalytic domain in 29 MPM patients.
- Functional assessment of mutation activating profiles using a COS-7 cell expression model.
- Clinical data analysis comparing survival in surgically treated patients (n=25) based on EGFR mutation status.
Main Results:
- Activating EGFR mutations were identified in 31% (9/29) of MPM patients, including 7 novel mutations and L858R.
- All identified missense mutations demonstrated activating potential and sensitivity to erlotinib.
- EGFR mut+ patients (n=7) had a lower rate of progressive disease (29%) and longer median survival (22 months) compared to EGFR mut- patients (n=18) (72% progressive disease, 14 months median survival).
Conclusions:
- Novel EGFR mutations in MPM are activating and responsive to erlotinib.
- MPM patients with activating EGFR mutations exhibit a relative survival benefit.
- Further investigation of EGFR mutations in a larger MPM cohort is warranted to explore erlotinib's therapeutic potential.
