Unknown

Dataset Information

0

Acquired resistance to EGFR-targeted therapies in colorectal cancer.


ABSTRACT: Cetuximab and panitumumab are anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibodies used as therapies for metastatic colorectal cancer patients. Intrinsic mechanisms of resistance, such as RAS mutations, can prevent patients from having a response with clinical benefit. The clinical efficacy of EGFR targeted antibodies is limited by the development of acquired (secondary) resistance, which typically occurs within 3-12 months from the start of therapy. Preclinical models and analyses of clinical samples have uncovered some of the alterations that confer a selective advantage to tumor cells when under the pressure of anti-EGFR therapy. Molecular profiling of clinical specimens confirmed that genetic alterations of genes in the EGFR-RAS-RAF-MEK signaling pathway and of receptor tyrosine kinases are mechanisms of acquired resistance to anti-EGFR antibodies. The escape from anti-EGFR blockade appears to converge on the (re)activation of MEK-ERK or AKT as revealed in preclinical studies. Circulating tumor DNA and patient derived xenografts have proven useful tools to monitor patients for resistance to anti-EGFR therapy and test combination therapies to overcome or reverse resistance.

SUBMITTER: Van Emburgh BO 

PROVIDER: S-EPMC5528615 | biostudies-other | 2014 Sep

REPOSITORIES: biostudies-other

Similar Datasets

| S-EPMC7140052 | biostudies-literature
| S-EPMC4055851 | biostudies-literature
| S-EPMC5026573 | biostudies-literature
| S-EPMC6407678 | biostudies-literature
| S-EPMC3436069 | biostudies-literature
| S-EPMC7463997 | biostudies-literature
| S-EPMC2670612 | biostudies-other
| S-ECPF-GEOD-38310 | biostudies-other
| S-EPMC4049336 | biostudies-literature
| S-EPMC9827113 | biostudies-literature