Molecular targets for tivantinib (ARQ 197) and vasculogenic mimicry in human melanoma cells

Kumar, Sudeep; Gajagowni, Saivaroon; Bryan, Jeffrey N.; Bodenhausen, Hannah M.

doi:10.1016/j.ejphar.2019.04.010

Cited by 11 publications

(7 citation statements)

References 34 publications

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“…Similar approaches have been reported for VM in melanoma. An interesting study by Kumar et al has showed that tivantinib alters proteins such as vinculin and RhoC to affect the cell cytoskeleton and morphology, and thereby decreases VM formed by melanoma cells in a 3D matrix [114]. Various traditional Chinese medicine have been reported to play critical roles in the treatment of malignant cancers.…”

Section: Clinical Significance Of Vm In Cancermentioning

confidence: 99%

Vasculogenic mimicry in carcinogenesis and clinical applications

et al. 2020

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Distinct from classical tumor angiogenesis, vasculogenic mimicry (VM) provides a blood supply for tumor cells independent of endothelial cells. VM has two distinct types, namely tubular type and patterned matrix type. VM is associated with high tumor grade, tumor progression, invasion, metastasis, and poor prognosis in patients with malignant tumors. Herein, we discuss the recent studies on the role of VM in tumor progression and the diverse mechanisms and signaling pathways that regulate VM in tumors. Furthermore, we also summarize the latest findings of non-coding RNAs, such as lncRNAs and miRNAs in VM formation. In addition, we review application of molecular imaging technologies in detection of VM in malignant tumors. Increasing evidence suggests that VM is significantly associated with poor overall survival in patients with malignant tumors and could be a potential therapeutic target.

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Section: Clinical Significance Of Vm In Cancermentioning

confidence: 99%

Vasculogenic mimicry in carcinogenesis and clinical applications

et al. 2020

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“…Although tivatinib was developed to inhibit MET, it recently showed an activity on microtubule polymerization indicating additional targets for this drug. As vasculogenic mimicry was reported for melanoma cells to mediate invasion and metastasis, Tivatinib was tested and found efficient in inhibiting cell viability, inducing apoptosis and reducing vasculogenic mimicry (Table 8) [171].…”

Section: Tivantinibmentioning

confidence: 99%

“…-Tivatinib increases vinculin in C8161 and UACC cells, RhoC in C8161 cells and reduces zyxin and FN1 mRNA in C8161 and UACC cells. -Tivatinib decreases VM formation in C8161 and WM793 cells.Kumar, S.R., et al 2019[171]…”

mentioning

confidence: 99%

RTK Inhibitors in Melanoma: From Bench to Bedside

Sabbah

Najem

Krayem

et al. 2021

Cancers

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MAPK (mitogen activated protein kinase) and PI3K/AKT (Phosphatidylinositol-3-Kinase and Protein Kinase B) pathways play a key role in melanoma progression and metastasis that are regulated by receptor tyrosine kinases (RTKs). Although RTKs are mutated in a small percentage of melanomas, several receptors were found up regulated/altered in various stages of melanoma initiation, progression, or metastasis. Targeting RTKs remains a significant challenge in melanoma, due to their variable expression across different melanoma stages of progression and among melanoma subtypes that consequently affect response to treatment and disease progression. In this review, we discuss in details the activation mechanism of several key RTKs: type III: c-KIT (mast/stem cell growth factor receptor); type I: EGFR (Epidermal growth factor receptor); type VIII: HGFR (hepatocyte growth factor receptor); type V: VEGFR (Vascular endothelial growth factor), structure variants, the function of their structural domains, and their alteration and its association with melanoma initiation and progression. Furthermore, several RTK inhibitors targeting the same receptor were tested alone or in combination with other therapies, yielding variable responses among different melanoma groups. Here, we classified RTK inhibitors by families and summarized all tested drugs in melanoma indicating the rationale behind the use of these drugs in each melanoma subgroups from preclinical studies to clinical trials with a specific focus on their purpose of treatment, resulted effect, and outcomes.

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“…It is likely that an alternate mechanism of action of tivantinib might have contributed to this observation. Although initially thought to be a selective MET inhibitor [ 39 ], the cell cytoskeleton proteins vinculin and RhoC in melanoma cells and Glycogen synthase kinase 3α/β (GSK3α/β) as a pro-tumorigenic signaling protein relevant in acute myeloid leukemia (AML) and lung cancer cells have been identified as molecular targets of tivantinib as well [ 40 , 41 , 42 ]. Besides c-MET, interference with other elements which are essential for resistance to cisplatin and osimertinib might therefore explain the diverging effects in the dose-dependent response between cabozantinib and tivantinib in relation to parental and resistant cells in our study.…”

Section: Discussionmentioning

confidence: 99%