MET receptor in oncology: From biomarker to therapeutic target

Malik, Raeva; Mambetsariev, Isa; Fricke, Jeremy; Chawla, Neal Shiv; Nam, Arin; Pharaon, Rebecca; Salgia, Ravi

doi:10.1016/bs.acr.2020.04.006

Cited by 20 publications

(19 citation statements)

References 204 publications

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“…MET , one of the receptor tyrosine kinases, is related to embryogenesis, organofaction, tumourigenesis, and cancer metastasis. Moreover, the aberrant expression of MET and its ligand, HGF, is associated with poor prognosis and drug resistance in cancers 49 50,51 .…”

Section: Discussionmentioning

confidence: 99%

MET inhibition enhances PARP inhibitor efficacy in castration‐resistant prostate cancer by suppressing the ATM/ATR and PI3K/AKT pathways

Zhou

Dai

Wang

et al. 2021

J Cellular Molecular Medi

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Up to 30% of patients with metastatic castration‐resistant prostate cancer (CRPC) patients carry altered DNA damage response genes, enabling the use of poly adenosine diphosphate–ribose polymerase (PARP) inhibitors in advanced CRPC. The proto‐oncogene mesenchymal–epithelial transition (MET) is crucial in the migration, proliferation, and invasion of tumour cells. Aberrant expression of MET and its ligand hepatocyte growth factor is associated with drug resistance in cancer therapy. Here, we found that MET was highly expressed in human CRPC tissues and overexpressed in DU145 and PC3 cells in a drug concentration‐dependent manner and is closely related to sensitivity to PARP inhibitors. Combining the PARP inhibitor olaparib with the MET inhibitor crizotinib synergistically inhibited CRPC cell growth both in vivo and in vitro. Further analysis of the underlying molecular mechanism underlying the MET suppression‐induced drug sensitivity revealed that olaparib and crizotinib could together downregulate the ATM/ATR signaling pathway, inducing apoptosis by inhibiting the phosphoinositide 3‐kinase/protein kinase B (PI3K/AKT) pathway, enhancing the olaparib‐induced antitumour effect in DU145 and PC3 cells. In conclusion, we demonstrated that MET inhibition enhances sensitivity of CRPC to PARP inhibitors by suppressing the ATM/ATR and PI3K/AKT pathways and provides a novel, targeted therapy regimen for CRPC.

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Section: Discussionmentioning

confidence: 99%

MET inhibition enhances PARP inhibitor efficacy in castration‐resistant prostate cancer by suppressing the ATM/ATR and PI3K/AKT pathways

Zhou

Dai

Wang

et al. 2021

J Cellular Molecular Medi

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“…MET (c-Met or HGFR) is the tyrosine kinase receptor for hepatocyte growth factor (HGF). This receptor-ligand interaction triggers classical RTK signaling pathways to promote cell migration, angiogenesis, and proliferation (reviewed in [146]). MET gain of function via overexpression, amplification, aberrant splicing, or mutations is associated with multiple cancer types, such as non-small cell lung carcinoma [147], gastrointestinal cancer [148], and hepatocellular carcinoma [149].…”

Section: Metmentioning

confidence: 99%

Systematic review of the receptor tyrosine kinase superfamily in neuroblastoma pathophysiology

Rozen

Shohet

2021

Cancer Metastasis Rev

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Background Neuroblastoma is a devastating disease accounting for 15% of all childhood cancer deaths. Yet, our understanding of key molecular drivers such as receptor tyrosine kinases (RTKs) in this pathology remains poorly clarified. Here, we provide a systematic analysis of the RTK superfamily in the context of neuroblastoma pathogenesis. Methods Statistical correlations for all RTK family members’ expression to neuroblastoma patient survival across 10 independent patient cohorts were annotated, synthesized, and ranked using the R2: Genomics Analysis and Visualization Platform. Gene expression of selected members across different cancer cell lines was further analyzed in the Cancer Cell Line Encyclopedia, part of the Cancer Dependency Map portal (depmap portal (http://depmap.org)). Finally, we provide a detailed literature review for highly ranked candidates. Results Our analysis defined two subsets of RTKs showing robust associations with either better or worse survival, constituting potential novel players in neuroblastoma pathophysiology, diagnosis, and therapy. We review the available literature regarding the oncogenic functions of these RTKs, their roles in neuroblastoma pathophysiology, and potential utility as therapeutic targets. Conclusions Our systematic analysis and review of the RTK superfamily in neuroblastoma pathogenesis provides a new resource to guide the research community towards focused efforts investigating signaling pathways that contribute to neuroblastoma tumor establishment, growth, and/or aggressiveness and targeting these druggable molecules in novel therapeutic strategies.

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“…High expression of the MET receptor has been shown to correlate with poor prognosis and resistance to therapy. MET exon 14 splicing variants that was initially identified in lung cancer can be treated through various tyrosine kinase inhibitors (TKIs) [11].…”

Section: Rtk Mutations: Targets For Cancer Therapymentioning

confidence: 99%

Recent Advances in the Therapeutic Development of Receptor Tyrosine Kinases (RTK) against Different Types of Cancer

Patranabis¹

2021

Biochemistry

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Receptor Tyrosine Kinases (RTKs) are an important class of receptors involved in regulating different cellular functions. The usual pathway of RTK activation involves specific ligand binding, dimerization and trans-autophosphorylation. Recently, RTK has been extensively studied as they have potential applications in targeted cancer therapy. RTK-based therapeutic strategies are promising because dysfunction of RTK is connected to a variety of diseases. More specifically, RTK has been widely associated with different types of cancer and related diseases. The chapter aims to cover recent advances and challenges in RTK related research, to get an overview of the problems and possibilities associated with targeted therapy. This will help in deciphering novel therapeutic applications in the future.

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MET receptor in oncology: From biomarker to therapeutic target

Cited by 20 publications

References 204 publications

MET inhibition enhances PARP inhibitor efficacy in castration‐resistant prostate cancer by suppressing the ATM/ATR and PI3K/AKT pathways

MET inhibition enhances PARP inhibitor efficacy in castration‐resistant prostate cancer by suppressing the ATM/ATR and PI3K/AKT pathways

Systematic review of the receptor tyrosine kinase superfamily in neuroblastoma pathophysiology

Recent Advances in the Therapeutic Development of Receptor Tyrosine Kinases (RTK) against Different Types of Cancer

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