Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.7.12.2 (
MEK
)
18,161
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Class 3
MEK1
mutations disrupt the negative regulatory helix region of
MEK1
and drive constitutive activation of both pMEK and pERK that is independent of RAF and of
MEK
phosphorylation. Targeting
MEK
with trametinib resulted in mixed clinical responses in class 3
MEK1
mutated Langerhans cell histiocytosis (LCH). The ERK inhibitor, ulixertinib, demonstrated limited anti-tumor activity in non-characterized
MEK1
mutated solid tumors, with 2 out 4 patients experiencing stable disease (SD). Here, we present the case of a 52-year-old female with
metastatic colon cancer
harboring a
MEK1
E102_I103del (class 3 mutation) who progressed on standard chemotherapy and showed no response to the
MEK
inhibitor trametinib, the ERK inhibitor ulixertinib, and the combination of ulixertinib and the anti-EGFR antibody panitumumab. Despite progressive disease (PD), the patient exhibited a steep but short-lived tumor marker response to
MEK
and ERK inhibition, suggesting the emergence of early mechanisms of resistance to MAPK pathway inhibition. This report presents the first case in the literature investigating a
MEK
inhibitor and an ERK inhibitor (alone and in combination with anti-EGFR therapy) in metastatic colorectal cancer harboring a class 3
MEK1
mutation (E102-I103 deletion).
...
PMID:A case of class 3
MEK1
mutated metastatic colorectal cancer with a non-durable tumor marker response to MEK and ERK inhibitors. 3194 31
