Nintedanib for the treatment of non-small-cell lung cancer

Rashdan, Sawsan; Hanna, Nasser H.

doi:10.1517/14656566.2014.897695

Cited by 11 publications

(6 citation statements)

References 46 publications

(23 reference statements)

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“…However, more recent clinical trials investigating VEGFR-2-targeted therapy demonstrated a relatively positive performance, without induction of hemoptysis, in patients exhibiting NSCLC containing squamous cell carcinoma ( 24 ). In addition, small molecule inhibitors of receptor tyrosine kinases, which work with VEGFR-2, nintedanib, sunitinib, sorafenib, vandetanib and vatalanib, have been tested as potential anticancer therapies ( 25 , 26 ). Due to the association between myoferlin and VEGFR-2 observed in the current study, the efficacy of myoferlin as a therapeutic agent may require further investigation.…”

Section: Discussionmentioning

confidence: 99%

Myoferlin expression in non-small cell lung cancer: Prognostic role and correlation with VEGFR-2 expression

Song

Lee

et al. 2015

Oncology Letters

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Myoferlin is a protein that is associated with cellular repair following injury. The expression of myoferlin in breast cancer and pancreatic adenocarcinoma has been reported to correlate with tumor invasiveness, epithelial to mesenchymal transition and an adverse prognosis. In the present study, myoferlin expression was investigated in non-small cell lung carcinoma (NSCLC), along with its association with patient prognosis and the expression of a number of other proteins. A total of 148 patients exhibiting NSCLC were enrolled in the present study. The survival data of all patients was examined, and myoferlin, vascular endothelial growth factor receptor-2 (VEGFR-2), epidermal growth factor receptor, E-cadherin, β-catenin, thyroid transcription factor-1 and tumor protein p63 expression was investigated via immunohistochemical staining of tissue microarrays. Myoferlin expression was detected in the cytoplasm of 75/148 (50.7%) of the NSCLC cases. In the adenocarcinoma cases, myoferlin-positive patients possessed a poorer prognosis (odds ratio, 2.94; P=0.339). In the squamous cell carcinoma cases, myoferlin expression was significantly associated with VEGFR-2 expression (P=0.001). Immunohistochemical staining for VEGFR-2 and myoferlin expression indicated similar features and cytoplasmic staining in tumor cells. As VEGFR-2 is a significant target for novel anticancer therapies, it is anticipated that myoferlin may also possess the potential to become a novel clinical target for the treatment of NSCLC.

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Section: Discussionmentioning

confidence: 99%

Myoferlin expression in non-small cell lung cancer: Prognostic role and correlation with VEGFR-2 expression

Song

Lee

et al. 2015

Oncology Letters

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“…Blocking the PDGFR signaling by either specific neutralizing antibodies that target the receptors or RTK inhibitors that disrupt the kinase activity has proven to have clinical efficacy in treating a number of human malignancies, including NSCLC. 35 – 38 Criteria for selecting candidate RTK inhibitors in cancer therapy include minimal toxicity and higher affinity with mutated forms of the kinase targets that are frequently present in cancer patients. Crenolanib, a potent RTK inhibitor with narrow and selective reactivity against both wild-type and mutated FLT3 and PDGFR (including PDGFRα and PDGFRβ), represents the first anticancer RTK inhibitor with predictably minimal toxicity.…”

Section: Discussionmentioning

confidence: 99%

Crenolanib, a PDGFR inhibitor, suppresses lung cancer cell proliferation and inhibits tumor growth in vivo

Wang¹,

Song

Ge³

et al. 2014

OTT

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Platelet-derived growth factor (PDGF) and its receptors (PDGFR), including PDGFRα and PDGFRβ, play important roles in tumorigenesis, tumor progression, and the regulation of stromal cell function. Constitutive activation of PDGFR signaling, gene rearrangement, and activating mutations of PDGFR have been identified in various types of human tumors and malignancies. PDGFRα and PDGFRβ belong to the family of type III receptor tyrosine kinases and, upon stimulation, activate downstream signaling cascades. Crenolanib is a specific tyrosine kinase inhibitor that targets and inhibits the kinase activity of PDGFR and the FMS-related tyrosine kinase 3. Its clinical efficacy in several human tumors is currently under investigation in Phase II clinical trials. In this study, we examined the potential role of crenolanib in the treatment of non-small-cell lung cancer (NSCLC). Using A549 cells as a model system, we have shown that crenolanib is capable of suppressing proliferation and inducing apoptosis in a dose-dependent manner. Crenolanib-treated cells have reduced migratory activity in response to inducers of chemotaxis. Furthermore, the in vivo antitumor activity of crenolanib was confirmed in an NSCLC xenograft tumor model. Injection of crenolanib significantly inhibited the growth of tumor mass by inducing apoptosis in tumor cells. Our results provide strong evidence supporting the use of crenolanib as a potential therapeutic agent in treating NSCLC. This work sets a foundation for further development of targeted and personalized therapeutics for lung cancer.

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“…Adenovirus-mediated overexpression of VEGF had no effect on aortic atherosclerotic plaque deposition or neovascularization [189], but systemic therapy with VEGF inhibitor led to accelerated atherogenesis [190]. Newer oncologic antiangiogenesis agents targeting combinations of the FGF, PDGF, and/or VEGF receptors have not demonstrated similar toxicities but evaluation in the treatment of peripheral arterial disease has not been pursued [191,192,193]. The long-term therapy required for a chronic disease such as peripheral artery disease may be another limiting factor in the utilization of these pharmaceuticals; therefore, research pursuing the more specific alternative of a selective MMP inhibitor to mitigate plaque neovascularization may be a more productive avenue.…”

Section: Targets To Promote Plaque Stabilizationmentioning

confidence: 99%

Multidimensional Contribution of Matrix Metalloproteinases to Atherosclerotic Plaque Vulnerability: Multiple Mechanisms of Inhibition to Promote Stability

Ruddy¹,

Ikonomidis²,

Jones³

2016

J Vasc Res

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The prevalence of atherosclerotic disease continues to increase, and despite significant reductions in major cardiovascular events with current medical interventions, an additional therapeutic window exists. Atherosclerotic plaque growth is a complex integration of cholesterol penetration, inflammatory cell infiltration, vascular smooth muscle cell (VSMC) migration, and neovascular invasion. A family of matrix-degrading proteases, the matrix metalloproteinases (MMPs), contributes to all phases of vascular remodeling. The contribution of specific MMPs to endothelial cell integrity and VSMC migration in atherosclerotic lesion initiation and progression has been confirmed by the increased expression of these proteases in plasma and plaque specimens. Endogenous blockade of MMPs by the tissue inhibitors of metalloproteinases (TIMPs) may attenuate proteolysis in some regions, but the progression of matrix degeneration suggests that MMPs predominate in atherosclerotic plaque, precipitating vulnerability. Plaque neovascularization also contributes to instability and, coupling the known role of MMPs in angiogenesis to that of atherosclerotic plaque growth, interest in targeting MMPs to facilitate plaque stabilization continues to accumulate. This article aims to review the contributions of MMPs and TIMPs to atherosclerotic plaque expansion, neovascularization, and rupture vulnerability with an interest in promoting targeted therapies to improve plaque stabilization and decrease the risk of major cardiovascular events.

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Nintedanib for the treatment of non-small-cell lung cancer

Abstract: Recent Phase III trials have shown promising efficacy results of nintedanib in NSCLC; however, many questions still need to be answered before it is put into routine use.

Cited by 11 publications

References 46 publications

Myoferlin expression in non-small cell lung cancer: Prognostic role and correlation with VEGFR-2 expression

Myoferlin expression in non-small cell lung cancer: Prognostic role and correlation with VEGFR-2 expression

Crenolanib, a PDGFR inhibitor, suppresses lung cancer cell proliferation and inhibits tumor growth in vivo

Multidimensional Contribution of Matrix Metalloproteinases to Atherosclerotic Plaque Vulnerability: Multiple Mechanisms of Inhibition to Promote Stability

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