Effects of lapatinib and trastuzumab on vascular endothelial growth factor in experimental corneal neovascularization

Kaya, Mehmet; Demır, Tamer; Bulut, Hakan; Akpolat, Nusret; Turgut, Burak

doi:10.1111/ceo.12500

Cited by 13 publications

(11 citation statements)

References 31 publications

(90 reference statements)

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“…While a direct influence of lapatinib on blood flow was not reported in the literature, an anti-angiogenic effect in lung cancer xenografts and an anti-vascular effect in a rat model for corneal neovascularization has been reported following lapatinib administration, purportedly through downregulation of VEGF [52,53]. Thus, the reduced blood flow following lapatinib treatment at day 7 for the lapatinib only group may be indicative of its anti-angiogenic and anti-vascular properties.…”

Section: Discussionmentioning

confidence: 91%

Liposomal Lapatinib in Combination with Low-Dose Photodynamic Therapy for the Treatment of Glioma

Fisher

Obaid

Niu

et al. 2019

JCM

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Background: Malignant gliomas are highly invasive and extremely difficult to treat tumours with poor prognosis and outcomes. Photodynamic therapy (PDT), mediated by Gleolan®, has been studied previously with partial success in treating these tumours and extending lifetime. We aim to determine whether combining PDT using ALA-protoporphyrin IX (PpIX) with a liposomal formulation of the clinical epidermal growth factor receptor (EGFR) inhibitor, lapatinib, would increase the anti-tumour PDT efficacy. Methods: Lapatinib was given in vitro and in vivo 24 h prior to PDT and for 3–5 days following PDT to elicit whether the combination provided any benefits to PDT therapy. Live-cell imaging, in vitro PDT, and in vivo studies were performed to elucidate the effect lapatinib had on PDT for a variety of glioma cell lines and as well as GSC-30 neurospheres in vivo. Results: PDT combined with lapatinib led to a significant increase in PpIX accumulation, and reductions in the LD50 of PpIX mediated PDT in two EGFR-driven cell lines, U87 and U87vIII, tested (p < 0.05). PDT + lapatinib elicited stronger MRI-quantified glioma responses following PDT for two human glioma-derived tumours (U87 and GSC-30) in vivo (p < 0.05). Furthermore, PDT leads to enhanced survival in rats following treatment with lapatinib compared to lapatinib alone and PDT alone (p < 0.05). Conclusions: As lapatinib is approved for other oncological indications, a realization of its potential combination with PDT and in fluorescence-guided resection could be readily tested clinically. Furthermore, as its use would only be in acute settings, long-term resistance should not pose an issue as compared to its use as monotherapy.

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Section: Discussionmentioning

confidence: 91%

Liposomal Lapatinib in Combination with Low-Dose Photodynamic Therapy for the Treatment of Glioma

Fisher

Obaid

Niu

et al. 2019

JCM

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“…Oral administration of lapatinib reduced corneal epithelial and stromal VEGF expression, which correlated with decreased CoNV in a rat silver-nitrate CoNV model. Lapatinib was more effective at preventing CoNV than the large monoclonal antibody against HER2, trastuzumab [41].…”

Section: Tyrosine Kinase Inhibitorsmentioning

confidence: 92%

“…For example, the combination of dovitinib and bevacizumab was no more effective at reducing CoNV than bevacizumab monotherapy [45]. Additionally, lapatinib in combination with trastuzumab showed equivocal results to lapatinib monotherapy [41]. hesperetin and antiangiogenic effect of sunitinib are believed to be the contributing factors to a greater therapeutic effect than monotherapy.…”

Section: Tyrosine Kinase Inhibitorsmentioning

confidence: 99%

Pharmacological Potential of Small Molecules for Treating Corneal Neovascularization

2020

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Under healthy conditions, the cornea is an avascular structure which allows for transparency and optimal visual acuity. Its avascular nature is maintained by a balance of proangiogenic and antiangiogenic factors. An imbalance of these factors can result in abnormal blood vessel proliferation into the cornea. This corneal neovascularization (CoNV) can stem from a variety of insults including hypoxia and ocular surface inflammation caused by trauma, infection, chemical burns, and immunological diseases. CoNV threatens corneal transparency, resulting in permanent vision loss. Mainstay treatments of CoNV have partial efficacy and associated side effects, revealing the need for novel treatments. Numerous natural products and synthetic small molecules have shown potential in preclinical studies in vivo as antiangiogenic therapies for CoNV. Such small molecules include synthetic inhibitors of the vascular endothelial growth factor (VEGF) receptor and other tyrosine kinases, plus repurposed antimicrobials, as well as natural source-derived flavonoid and non-flavonoid phytochemicals, immunosuppressants, vitamins, and histone deacetylase inhibitors. They induce antiangiogenic and anti-inflammatory effects through inhibition of VEGF, NF-κB, and other growth factor receptor pathways. Here, we review the potential of small molecules, both synthetics and natural products, targeting these and other molecular mechanisms, as antiangiogenic agents in the treatment of CoNV.

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“…In recent studies, both substances were compared for the treatment of experimental corneal angiogenesis. The results suggested that systemically administered lapatinib is more efective than systemically administered trastuzumab in preventing corneal angiogenesis [74].…”

Section: Tyrosine Kinase Inhibitorsmentioning

confidence: 99%

Corneal Angiogenesis: Etiologies, Complications, and Management

Feizi¹

2017

Physiologic and Pathologic Angiogenesis - Signaling Mechanisms and Targeted Therapy

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A large subset of corneal pathologies involves the formation of new blood vessels, leading to compromised visual acuity. Additionally, neovascularization of the cornea worsens the prognosis of subsequent penetrating keratoplasty, keeping the patient in a vicious circle of poor prognosis. Ocular angiogenesis results from the upregulation of proangiogenic and downregulation of antiangiogenic factors. There is a tremendous need for developing efective measures to prevent and/or treat corneal neovascularization. Topical steroid medication, cautery, argon and yellow dye laser, and ine needle diathermy have all been advocated with varying degrees of success. The process of corneal neovascularization is primarily mediated by the vascular endothelial growth factor family of proteins, and current therapies are aimed at disrupting the various steps in this pathway. This article aims to review the clinical causes and presentations of corneal neovascularization caused by diferent etiologies. Moreover, this chapter reviews diferent complications caused by corneal neovascularization and summarizes the most relevant treatments available so far.

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Effects of lapatinib and trastuzumab on vascular endothelial growth factor in experimental corneal neovascularization

Abstract: It is suggested that systemically administered lapatinib is more effective than systemically administered trastuzumab in preventing corneal neovascularization.

Cited by 13 publications

References 31 publications

Liposomal Lapatinib in Combination with Low-Dose Photodynamic Therapy for the Treatment of Glioma

Liposomal Lapatinib in Combination with Low-Dose Photodynamic Therapy for the Treatment of Glioma

Pharmacological Potential of Small Molecules for Treating Corneal Neovascularization

Corneal Angiogenesis: Etiologies, Complications, and Management

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