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Ref Type Journal Article
PMID (32332018)
Authors Sun W, Li SC, Xu L, Zhong W, Wang ZG, Pan CZ, Li J, Jin GZ, Ta N, Dong W, Liu D, Liu H, Wang HY, Ding J
Title High FLT3 Levels May Predict Sorafenib Benefit in Hepatocellular Carcinoma.
Journal Clinical cancer research : an official journal of the American Association for Cancer Research
Vol
Issue
Date 2020 Apr 24
URL
Abstract Text To identify a predictive biomarker of sorafenib for hepatocellular carcinoma personalized therapy.The patients treated with or without sorafenib after hepatocellular carcinoma recurrence from multicenters were matched with propensity score matching analysis. The expression levels of Fms-like tyrosine kinase 3 (FLT3) in hepatocellular carcinoma specimens of the matched patients (n = 276) were analyzed by IHC. The optimal cut-off point of FLT3 levels for overall survival (OS) was defined via Cutoff Finder. Subgroup analysis of OS was employed to investigate the association between FLT3 levels and sorafenib benefit. The predictive value was assessed via Cox regression models with an interaction term. Hepatocellular carcinoma and paratumoral normal tissues were used to investigate the expression and copy-number variation of FLT3. Patient-derived xenograft (PDX) models were used to confirm the association between FLT3 levels and sorafenib response.Patients with FLT3-high hepatocellular carcinoma exhibited a superior OS upon sorafenib treatment. High FLT3 levels were predictive of sorafenib benefit in terms of OS (Pinteraction = 0.00006). Copy-number losses and decreased expression of FLT3 in hepatocellular carcinoma were detected in about 64% of patients. Moreover, the PDXs derived from tumors with high FLT3 levels also displayed a better response to sorafenib.Sorafenib may be able to delay tumor progression in patients with FLT3-high hepatocellular carcinoma. This potential biomarker needs to be further validated in independent cohorts prior to helping stratify patients for precision therapy in advanced hepatocellular carcinoma.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
FLT3 over exp hepatocellular carcinoma sensitive Sorafenib Preclinical - Pdx Actionable In a preclinical study, Nexavar (sorafenib) inhibited tumor growth and reduced the percentage of tumor cells expressing Ki-67 in patient-derived xenograft (PDX) models of hepatocellular carcinoma harboring FLT3 overexpression, but had no effect on tumor growth inhibition or Ki-67 expression compared to control treatments in PDX models of HCC harboring decreased FLT3 expression (PMID: 32332018). 32332018
FLT3 over exp hepatocellular carcinoma sensitive Sorafenib Clinical Study Actionable In an observational clinical study, hepatocellular carcinoma patients harboring FLT3 overexpression treated with Nexavar (sorafenib) demonstrated improved overall survival (24.9 months (n=67)) when compared to patients with FLT3 overexpression who received a control treatment (10.0 months (n=49)) or patients with decreased FLT3 expression treated with Nexavar (sorafenib) (16.0 months (n=71)) (PMID: 32332018). 32332018