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: UMLS:C0476089 (
endometrial cancer
)
11,379
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Development of resistance causes failure of drugs targeting receptor tyrosine kinase (RTK) networks and represents a critical challenge for precision medicine. Here, we show that
PHLDA1
downregulation is critical to acquisition and maintenance of drug resistance in RTK-driven cancer. Using fibroblast growth factor receptor (FGFR) inhibition in
endometrial cancer
cells, we identify an Akt-driven compensatory mechanism underpinned by downregulation of
PHLDA1
. We demonstrate broad clinical relevance of our findings, showing that
PHLDA1
downregulation also occurs in response to RTK-targeted therapy in breast and renal cancer patients, as well as following trastuzumab treatment in HER2
+
breast cancer cells. Crucially, knockdown of
PHLDA1
alone was sufficient to confer de novo resistance to RTK inhibitors and induction of
PHLDA1
expression re-sensitized drug-resistant cancer cells to targeted therapies, identifying
PHLDA1
as a biomarker for drug response and highlighting the potential of
PHLDA1
reactivation as a means of circumventing drug resistance.
...
PMID:PHLDA1 Mediates Drug Resistance in Receptor Tyrosine Kinase-Driven Cancer. 2949 Feb 81
