Cancer Cells Expressing Oncogenic Rat Sarcoma Show Drug-Addiction Toward Epidermal Growth Factor Receptor Antibodies Mediated by Sustained MAPK Signaling.

ABSTRACT: Epidermal growth factor receptor (EGFR) antibodies may have detrimental effects in patients with metastatic colorectal cancer expressing oncogenic Rat sarcoma (RAS). Since a significant number of patients acquire RAS-mediated resistance during EGFR-directed treatment, understanding the molecular mechanism underlying these antibody-mediated tumor-promoting effects is of relevance to design more resistance-preventive treatment approaches. To test this, we set up a Ba/F3 cellular model system transformed to EGFR/RAS dependency to be able to study proliferation, RAS activity as well as MAPK signaling upon inhibition of wild-type RAS isoforms by therapeutic EGFR antibodies. Here, we show that the EGFR antibodies cetuximab and panitumumab induce paradoxical stimulation and enhance proliferation

SUBMITTER: Tintelnot J 

PROVIDER: S-EPMC6985072 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature