Ocular toxicities are among the most common adverse events resulting from targeted anticancer agents and are becoming increasingly relevant in the management of patients on these agents. The purpose of this study is to provide a framework for management of these challenging toxicities based on objective data from FDA labels and from analysis of the literature. All oncologic drugs approved by the FDA up to March 14, 2015, were screened for inclusion. A total of 16 drugs (12 small-molecule drugs and 4 monoclonal antibodies) were analyzed for ocular toxicity profiles based on evidence of ocular toxicity. Trials cited by FDA labels were retrieved, and a combination search in Medline, Google Scholar, the Cochrane database, and the NIH Clinical Trials Database was conducted. The majority of ocular toxicities reported were low severity, and the most common were conjunctivitis and "visual disturbances." However, severe events including incidents of blindness, retinal vascular occlusion, and corneal ulceration occurred. The frequency and severity at which ocular toxicities occur merits a more multidisciplinary approach to managing patients with agents that are known to cause ocular issues. We suggest a standardized methodology for referral and surveillance of patients who are potentially at risk of severe ocular toxicity.
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http://dx.doi.org/10.18632/oncotarget.17634 | DOI Listing |
Sci Rep
January 2025
Department of Chemistry and Biochemistry, The University of Notre Dame, 305 McCourtney Hall, Notre Dame, IN, 46556, USA.
The heat shock protein 90 (Hsp90) family of molecular chaperones mediates the folding and activation of ~ 400 client proteins, many of which contribute to oncogenesis. As a result, Hsp90 pan-inhibitors, which inhibit all four Hsp90 isoforms, have been investigated in the clinic for the treatment of cancer. Unfortunately, detrimental side effects were observed and hindered the clinical development of pan-Hsp90 inhibitors.
View Article and Find Full Text PDFBioorg Chem
January 2025
Department of Chemistry, St Berchmans College (Autonomous), Changanassery, Kerala 686101, India; Centre for Theoretical and Computational Chemistry, St Berchmans College (Autonomous), Changanassery, Kerala 686101, India. Electronic address:
In this study, three novel derivatives of benzo[b]thiophene-2-carbaldehyde (BTAP1, BTAP2, and BTAP3) were successfully synthesized and comprehensively characterized using spectroscopic techniques including FTIR, UV-VIS, HNMR, and CNMR. Thermal analysis through TGA and DTA demonstrated remarkable thermal stability with a maximum threshold at 270 °C. Spectroscopic investigations revealed π → π* transitions in all compounds, attributed to the conjugated system comprising benzothiophene rings connected to bromophenyl/ aminophenyl/phenol rings via α, β-unsaturated ketone bridges.
View Article and Find Full Text PDFJ Vis Exp
January 2025
Departments of Ophthalmology and Anatomy and Cell Biology, Kresge Eye Institute, Wayne State University School of Medicine;
Due to its anatomical and physiological similarities to the human eye, the porcine eye serves as a robust model for biomedical research and ocular toxicity assessment. An air/liquid corneal culture system using porcine eyes was developed, and ex vivo epithelial wound healing was utilized as a critical parameter for these studies. Fresh pig corneas were processed for organ culture, with or without epithelial wounding.
View Article and Find Full Text PDFTransl Vis Sci Technol
January 2025
STZ eyetrial at the Centre for Ophthalmology, Tuebingen, Germany.
Purpose: Reports of gene therapy-associated retinal atrophies and inflammation have highlighted the importance of preclinical safety assessments of adeno-associated virus (AAV) vector systems. We evaluated in nonhuman primates (NHPs) the ocular safety and toxicology of a novel AAV gene therapy targeting retinitis pigmentosa caused by mutations in PDE6A, which has since been used in a phase I/II clinical trial (NCT04611503).
Methods: A total of 34 healthy cynomolgus animals (Macaca fascicularis) were treated with subretinal injections of rAAV.
Gynecol Oncol Rep
February 2025
Department of Ophthalmology and Visual Science, University of Chicago, Chicago, IL, United States.
Introduction: To report a series of patients who developed ocular surface disease related to tisotumab vedotin-tftv (TV), an antibody-drug conjugate (ADC) approved for the treatment of recurrent or metastatic cervical cancer.
Methods: This was a multicenter retrospective chart review study of patients who developed ocular surface disease related to TV between April 1st, 2022 to August 31st, 2023.
Results: Five patients were identified who developed ocular surface disease while on TV.
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