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Last update 08 May 2025

FRK

Last update 08 May 2025

Basic Info

Synonyms

FRK, fyn related Src family tyrosine kinase, FYN-related kinase

+ [8]

Introduction

Non-receptor tyrosine-protein kinase that negatively regulates cell proliferation. Positively regulates PTEN protein stability through phosphorylation of PTEN on 'Tyr-336', which in turn prevents its ubiquitination and degradation, possibly by reducing its binding to NEDD4. May function as a tumor suppressor.

Drugs associated with FRK

Regorafenib

Target

ABL x BRAF x BRAF V600E x CRAF x CSF-1R x DDR2 x EphA2 x FGFR1 x FGFR2 x FRK x MAPK11 x PDGFRα x PDGFRβ x RET x Tie-2 x TrkA x VEGFR1 x VEGFR2 x VEGFR3 x c-Kit

Mechanism

ABL inhibitors [+19]

Active Org.

Merck KGaA [+9]

Originator Org.

Bayer AG

Active Indication

Liver Cancer [+53]

Inactive Indication

Advanced Bile Duct Carcinoma [+23]

Drug Highest PhaseApproved

First Approval Ctry. / Loc.

United States

First Approval Date27 Sep 2012

358

Clinical Trials associated with FRK

NCT06820957

/ Not yet recruitingPhase 2/3IIT

Randomized Phase 2/3 Trial of Vincristine-Irinotecan-Regorafenib in Combination With Vincristine-Doxorubicin-Cyclophosphamide (VDC) and Ifosfamide-Etoposide (IE) in Patients With Newly Diagnosed Metastatic Ewing Sarcoma

This phase II/III trial compares the effect of vincristine, irinotecan, and regorafenib (VIrR) in combination with vincristine, doxorubicin, cyclophosphamide (VDC), ifosfamide and etoposide (IE) to usual treatment with VDC/IE for the treatment of newly diagnosed Ewing sarcoma or other round cell sarcomas that have spread from where they first started (primary site) to other places in the body (metastatic). Vincristine is in a class of medications called vinca alkaloids. It works by stopping tumor cells from growing and dividing and may kill them. Irinotecan is in a class of antineoplastic medications called topoisomerase I inhibitors. It blocks a certain enzyme needed for cell division and deoxyribonucleic acid (DNA) repair and may kill tumor cells. Regorafenib, a type of kinase inhibitor and a type of antiangiogenesis agent, blocks certain proteins, which may help keep tumor cells from growing. It may also prevent the growth of new blood vessels that tumors need to grow. Doxorubicin is in a class of medications called anthracyclines. Doxorubicin damages the cell's DNA and may kill tumor cells. It also blocks a certain enzyme needed for cell division and DNA repair. Cyclophosphamide is in a class of medications called alkylating agents. It works by damaging the cell's DNA and may kill tumor cells. It may also lower the body's immune response. Ifosfamide, a type of alkylating agent and a type of antimetabolite, attaches to DNA in cells and may kill tumor cells. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and DNA repair and may kill tumor cells. Giving VIrR/VDC/IE may be more effective than usual treatment with VDC/IE in treating patients with newly diagnosed metastatic Ewing sarcoma or other round cell sarcomas.

Start Date15 Jul 2025

Sponsor / Collaborator

The Children's Oncology Group Foundation, Inc.

NCT06946849

/ Not yet recruitingPhase 2IIT

Second-line Regimen Combined With Radiotherapy Versus Without Radiotherapy in Patients With Locally Advanced/Oligometastatic Intrahepatic Cholangiocarcinoma After Failure of First-line Treatment：an Open-label, Randomized, Controlled Phase II Clinical Study

Second-line regimen with or without consolidative radiotherapy in patients with oligometastatic/locally advanced unresectable intrahepatic cholangiocarcinoma: an open-label, randomised, controlled study.

Start Date01 Jun 2025

Sponsor / Collaborator-

NCT06902246

/ Not yet recruitingPhase 2IIT

Regorafenib and Yttrium-90 Radioembolization for Treatment of Unresectable Hepatocellular Carcinoma

The purpose of this study is to determine the effects that Regorafenib in combination with Yttrium-90 (Y-90) radioembolization has on patients with unresectable hepatocellular carcinoma.

Start Date01 Jun 2025

Sponsor / Collaborator

University of Miami

[+1]

100 Clinical Results associated with FRK

100 Translational Medicine associated with FRK

0 Patents (Medical) associated with FRK

303

Literatures (Medical) associated with FRK

01 Apr 2025·Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

Development and validation of a kinase-related gene signature as a novel diagnostic and prognostic model for prostate cancer

Article

Author: Wang, Qi ; Wei, Weiyang ; Zhu, Haiying ; Huang, Yaqiang ; Liang, Yingke ; Zhong, Weide ; Liang, Zhenguo ; Mo, Rujun ; Huang, Hongxing ; He, Huichan ; Ye, Jianheng ; Dai, Qishan ; Yang, Hao

BACKGROUNDProstate cancer (PCa) is a prevalent malignant tumor in men worldwide. Kinases play a key role in the development of multiple tumors. Nevertheless, the role of kinases in PCa remains largely unclear.METHODSA kinase-related gene signature was constructed by LASSO Cox regression analysis using the TCGA_PRAD cohort. The diagnostic and prognostic values of the signature were then evaulated. Furthermore, a loss-of-function assay was carried out to explore the function of NEK5 in PCa.RESULTSA signature of 13 kinase-related genes (NEK5, FRK, STK39, STYK1, IGF1R, RPS6KC1, TTK, CDK1, NEK2, PTK6, DAPK1, MELK and EPHA10) was constructed. The PCa patients presenting a high-risk score according to the signature demonstrated poorer disease-free survival compared to those with a low score. Additionally, TMB was found to be remarkably increased in patients categorized as high-risk relative to low-risk patients. Moreover, the 13-gene signature may also have good predictive value for PCa diagnosis. Furthermore, NEK5 expression was remarkably elevated in PCa tissues relative to benign tissues. NEK5 deficiency significantly inhibited PCa cell growth and suppressed mitochondrial OXPHOS.CONCLUSIONThe 13-gene signature constructed in this study may exhibit good performance in PCa diagnosis and prognosis evaluation. We identified the oncogenic role of NEK5 in PCa. NEK5 may serve as a therapeutic target for treatting PCa.

01 Mar 2025·Molecular and Cellular Biochemistry

The BCR::ABL1 tyrosine kinase inhibitors ponatinib and nilotinib differentially affect endothelial angiogenesis and signalling

Article

Author: Zibrova, Darya ; Ernst, Thomas ; Hochhaus, Andreas ; Heller, Regine

AbstractBCR::ABL1 inhibitors, the treatment of choice for the majority of patients with chronic myeloid leukaemia (CML), can cause vascular side effects that vary between agents. The exact underlying mechanisms are still poorly understood, but the vascular endothelium has been proposed as a site of origin. The present study investigates the effects of three BCR::ABL1 inhibitors, ponatinib, nilotinib and imatinib, on angiogenesis and signalling in human endothelial cells in response to vascular endothelial growth factor (VEGF). The experiments were performed in endothelial cells isolated from human umbilical veins. After exposure to imatinib, ponatinib and nilotinib, the angiogenic capacity of endothelial cells was assessed in spheroid assays. VEGF-induced signalling pathways were examined in Western blotting experiments using different specific antibodies. RNAi technology was used to downregulate proteins of interest. Intracellular cGMP levels were measured by ELISA. Imatinib had no effect on endothelial function. Ponatinib inhibited VEGF-induced sprouting, while nilotinib increased spontaneous and VEGF-stimulated angiogenesis. These effects did not involve wild-type ABL1 or ABL2, as siRNA-mediated knockdown of these kinases did not affect angiogenesis and VEGF signalling. Consistent with their effects on sprouting, ponatinib and nilotinib affected angiogenic pathways in opposite directions. While ponatinib inhibited VEGF-induced signalling and cGMP formation, nilotinib activated angiogenic signalling, in particular phosphorylation of extracellular signal-regulated kinase 1/2 (Erk1/2). The latter occurred in an epidermal growth factor receptor (EGFR)-dependent manner possibly via suppressing Fyn-related kinase (FRK), a negative regulator of EGFR signalling. Both, pharmacological inhibition of Erk1/2 or EGFR suppressed nilotinib-induced angiogenic sprouting. These results support the notion that the vascular endothelium is a site of action of BCR::ABL1 inhibitors from which side effects may arise, and that the different vascular toxicity profiles of BCR::ABL1 inhibitors may be due to their different actions at the molecular level. In addition, the as yet unknown pro-angiogenic effect of nilotinib should be considered in the treatment of patients with comorbidities associated with pathological angiogenesis, such as ocular disease, arthritis or obesity.

01 Feb 2025·Human Pathology

Systemic ALK-negative anaplastic large cell lymphoma: Insights into morphologic, immunophenotypic, genetic and molecular characteristics

Review

Author: Medeiros, L Jeffrey ; Xu, Jie ; Fan, Guang ; Li, Shaoying ; Medeiros, L. Jeffrey ; Xie, Wei

Anaplastic large cell lymphoma (ALCL) is a mature T-cell neoplasm characterized by large pleomorphic cells, often with horseshoe- or kidney-shaped nuclei and abundant cytoplasm (hallmark cells), and uniformly strong CD30 expression. Based on ALK expression or ALK rearrangement, ALCL is further classified into ALK-positive (ALK+) and ALK-negative types. This review focuses on the clinicopathologic, immunophenotypic, cytogenetic and molecular features of systemic ALK-negative ALCL. These patients are usually older adults who present with advanced stage disease and often a poor prognosis. ALK-negative ALCL is morphologically indistinguishable from the common pattern of ALK+ ALCL, but some cases show non-common morphology, such as "donut cells", Hodgkin-like features. ALK-negative ALCL is often negative for T-cell antigens (so-called "antigen loss") and in some cases can have a "null" immunophenotype and be confused with other hematopoietic and non-hematopoietic neoplasms. Recurrent genetic/molecular alterations have been identified in systemic ALK-negative ALCL, including rearrangements of DUSP22, TP63, JAK2, FRK, MYC, ROS1 and TYK2; mutations of JAK1, STAT3 and MSCE; and aberrant expression of ERBB4. Some of these alterations may have prognostic significance and/or provide potential therapeutic targets. Data support the idea that ALK-negative ALCL with DUSP22 rearrangement is a distinctive variant due to its unique morphologic, immunophenotypic and molecular features. Gene expression profiling data have shown that ALK-negative ALCL has distinctive molecular signatures, different from ALK+ ALCL and other T-cell lymphomas. Better understanding of the morphologic, immunophenotypic, genetic and molecular features of ALK-negative ALCL will help establish the correct diagnosis, guide therapeutic strategies and improve patient outcomes.

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