Pimasertib‐associated ophthalmological adverse events

Dijk, Elon H. C. van; Kruit, Wim; Jager, Martine J.; Luyten, Gregorius P M; Vingerling, Johannes R.; Boon, Camiel J F

doi:10.1111/aos.13677

Cited by 7 publications

(3 citation statements)

References 29 publications

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“…Other reported features of MEKAR include the thickening of the ellipsoid zone and a "starry sky" pattern of distribution of subretinal granular deposits, with suspected photoreceptor/ RPE toxicity and dysfunction [221]. These effects seem to be function-specific to the MEK inhibition itself and not compound side-effects from alternative actions, as the same clinical observations with the same levels of MEKAR severity have been also observed in patients receiving pimasertib [222] or cobimetinib (a MEK inhibitor), which was manageable in the latter case even without a dose modification, and with no visual loss or permanent retinal damage being detected [223].…”

Section: Mapk Inhibitoradverse Effectsmentioning

confidence: 64%

MAPK Pathways in Ocular Pathophysiology: Potential Therapeutic Drugs and Challenges

Moustardas

Aberdam

Lagali

2023

Cells

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Mitogen-activated protein kinase (MAPK) pathways represent ubiquitous cellular signal transduction pathways that regulate all aspects of life and are frequently altered in disease. Once activated through phosphorylation, these MAPKs in turn phosphorylate and activate transcription factors present either in the cytoplasm or in the nucleus, leading to the expression of target genes and, as a consequence, they elicit various biological responses. The aim of this work is to provide a comprehensive review focusing on the roles of MAPK signaling pathways in ocular pathophysiology and the potential to influence these for the treatment of eye diseases. We summarize the current knowledge of identified MAPK-targeting compounds in the context of ocular diseases such as macular degeneration, cataract, glaucoma and keratopathy, but also in rare ocular diseases where the cell differentiation, proliferation or migration are defective. Potential therapeutic interventions are also discussed. Additionally, we discuss challenges in overcoming the reported eye toxicity of some MAPK inhibitors.

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Section: Mapk Inhibitoradverse Effectsmentioning

confidence: 64%

MAPK Pathways in Ocular Pathophysiology: Potential Therapeutic Drugs and Challenges

Moustardas

Aberdam

Lagali

2023

Cells

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“…Some reports described the occurrence of outer retinal layer separation in subjects treated with selumetinib or pimasertib for astrocytoma and ovarian cancer, respectively. Visual symptoms appeared six months after starting selumetinib and a few days after the administration of pimasertib (60 mg/day), with a spontaneous, without visual sequelae, resolution of the retinal detachment after drugs discontinuation [37,38] . Interestingly, the retreatment with selumetinib determined the relapse of these findings.…”

Section: Targeted Anticancer Therapymentioning

confidence: 99%

Cancer drugs and diabetic retinopathy: a dangerous, underestimated association

Milluzzo,

Manuella,

Frittitta

et al. 2024

Metab Target Organ Damage

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The worldwide growing prevalence of diabetes and cancer led to an increase in subjects affected by both these diseases that share several of the involved risk factors and have a complex, multifactorial etiopathogenesis. Cancer therapies could have harmful effects on several organs, particularly in subjects also affected by diabetes and its related comorbidities. Moreover, cancer diagnosis often monopolizes the attention of both patients and caregivers, thus reducing the attention to pre-existent diseases. Retinopathy is one of the most frequent microvascular complications of diabetes, accounting for about 5% of legal blindness worldwide. The retinal neurovascular unit is dysfunctional in diabetes and could represent a frail site when cancer therapies are administered. Nevertheless, the short- and long-term effects of the different anticancer molecules on retinal tissue, especially in diabetic subjects, are poorly known, and no specific recommendations on their prevention and management are available. In this review, we summarised the current data on this topic, focusing on the different cancer class drugs involved in retinal damage: anti-oestrogen, classical cytolytic chemotherapy (alkylating agents, taxanes, topoisomerase inhibitors, and antimetabolites), mitogen-activated protein kinase, tyrosine-kinase, and vascular endothelial growth factor inhibitors are the cancer drugs associated with retinal damage and visual disturbance. However, further studies are necessary to improve knowledge on the molecular and clinical relation between cancer therapies and retinopathy, in order to provide clinicians with evidence-based protocols to optimise the management of these conditions and minimise vision loss occurrence, impaired quality of life, and public health expense.

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“…En una cohorte prospectiva que se llevó a cabo en los Países Bajos se analizaron los efectos adversos del tratamiento con pimasertib en pacientes con melanoma cutáneo metastásico encontrando presencia de líquido seroso subretiniano en la totalidad de los pacientes, nueve a 27 días después del inicio del tratamiento, así como también oclusión de la vena retiniana bilateral 23 .…”

Section: Pimasertibunclassified

Toxicidad retiniana inducida por nuevos antineoplásicos. Revisión de la literatura

López-Puerto¹,

Quijano-Nieto²,

Otoya-Albino³

2022

RSCO

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Introducción: Los nuevos antineoplásicos son medicamentos innovadores en el tratamiento del cáncer. Actualmente hay poca información sobre la seguridad y efectos adversos de estos medicamentos a nivel retiniano. Es importante conocer estos efectos para prevenir pérdida de visión en pacientes oncológicos. Objetivo: Definir cuáles son los hallazgos de toxicidad retiniana en los usuarios de nuevos antineoplásicos. Diseño del estudio: Revisión de la literatura. Métodos: Se realizó una búsqueda de literatura en PubMed, Embase, Cochrane, Scielo y literatura gris con términos MeSH: "toxicity" AND "retina" AND "drugs" AND/OR "MEK inhibitors", "BRAF inhibitors", "checkpoint inhibitors". Se seleccionaron 16 artículos para análisis y extracción de datos. Resultados: Existen múltiples efectos adversos reportados en la literatura, los más comunes son desprendimiento de retina exudativo y seroso asociado a la presencia de líquido subretiniano, oclusión de vena central de retina y alteraciones vasculares. La patología más estudiada ha sido melanoma metastásico y la terapia que más presenta efectos adversos ha sido la combinada MEK-BRAF.

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Pimasertib‐associated ophthalmological adverse events

Cited by 7 publications

References 29 publications

MAPK Pathways in Ocular Pathophysiology: Potential Therapeutic Drugs and Challenges

MAPK Pathways in Ocular Pathophysiology: Potential Therapeutic Drugs and Challenges

Cancer drugs and diabetic retinopathy: a dangerous, underestimated association

Toxicidad retiniana inducida por nuevos antineoplásicos. Revisión de la literatura

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