Avapritinib efficacy in primary hepatic neuroendocrine carcinoma with elevated PDGFRA expression: Insights from a PDX model study.
Biochem Biophys Res Commun
; 736: 150504, 2024 Aug 06.
Article
in En
| MEDLINE
| ID: mdl-39121673
ABSTRACT
BACKGROUND & AIMS:
Primary Hepatic Neuroendocrine Carcinoma (PHNEC) is a rare and aggressive tumor with high recurrence rates. Surgical resection remains the only therapeutic strategy. The effectiveness of tyrosine kinase inhibitors (TKIs) for PHNEC remains unclear due to limited research.METHODS:
We employed immunohistochemical staining to diagnose PHNEC and assess the expression of eight tyrosine kinase receptors in tumor tissues, including VEGFRs, PDGFRA, EGFR, FGFRs et al. A patient-derived xenograft (PDX) model was established using PHNEC tumor tissues to test the efficacy of TKIs. PDX mice bearing tumors were treated with Avapritinib, an FDA-approved PDGFRA-targeting drug, at a daily oral dose of 10 mg/kg for 2 weeks.RESULTS:
Pathological analysis confirmed the diagnosis of PHNEC with positive expression of Neural cell adhesion molecule (NCAM/CD56), Synaptophysin (Syn), and Somatostatin receptor 2 (SSTR-2), and negative expression of Hep (Hepatocyte Paraffin 1), a biomarker for Hepatocellular carcinoma. Notably, PDGFRA was significantly overexpressed in PHNEC tumor tissues compared to other tyrosine kinases. Avapritinib treatment significantly reduced tumor growth in PDX mice by 73.9 % (p = 0.008). Additionally, Avapritinib treatment led to a marked decrease in PDGFRA and Ki-67 expression, suggesting that it inhibits tumor cell proliferation by suppressing PDGFRA.CONCLUSION:
Our findings suggest that PDGFRA is a potential therapeutic target for PHNEC, and its inhibition with Avapritinib may offer clinical benefits to patients with this rare malignancy.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Biochem Biophys Res Commun
Year:
2024
Document type:
Article
Country of publication:
Estados Unidos