Understanding antibody-drug conjugates (ADCs): A paradigm shift in cancer therapy
ADCs represent a significant leap in targeted cancer treatment. Combining monoclonal antibodies with cytotoxic agents, these drugs are engineered to deliver their potent payloads directly to tumor cells while sparing healthy tissues.
"ADCs may represent a paradigm shift in cancer treatment," Dr. Farooq said, referencing an article from The Lancet in 2019, that underscored the precision of this approach compared to traditional chemotherapies.
While these innovations have opened new therapeutic horizons, they have also introduced unique ocular challenges. Dr. Farooq shared his first encounter with an ADC-related case during his cornea fellowship in 2015. Since then, the evolving role of ADCs has shed light on their ocular side effects, including corneal epithelial microcysts, dry eye and conjunctival changes.
Unpacking ocular toxicities
Dr. Farooq’s presentation delved into the complex ocular effects associated with ADCs:
- Corneal epithelial microcysts or lesions: Often seen in the periphery, these lesions can migrate centrally with continued ADC exposure. Intriguingly, Dr. Farooq noted that some microcysts halt before reaching the central cornea, potentially due to epithelial cells dying before making it to the center.
- Reversibility and variability: The good news is that these changes can reverse upon cessation of treatment, though the timeline varies significantly between patients.
- Other manifestations: Limbal stem cell dysfunction, dry eye symptoms and conjunctival subepithelial fibrosis have been observed, with varying severity and frequency depending on the specific ADC.
Bridging mechanisms to clinical implications
The webinar highlighted the potential mechanisms of ADC-induced ocular toxicity, including on-target and off-target effects. For example, HER2-targeting ADCs might inadvertently impact the cornea, where HER2 is expressed. Conversely, off-target effects may arise from non-specific cellular uptake processes, such as macropinocytosis.
Dr. Farooq highlighted emerging research exploring ways to mitigate these toxicities.
"There’s evidence that certain FDA-approved drugs can inhibit macropinocytosis," he noted, referencing studies that identified imipramine, phenoxybenzamine and vinblastine as potential therapeutic agents.
Collaboration and future directions
Recognizing the growing prevalence of ADC-related ocular cases, Dr. Farooq emphasized the importance of collaboration. A new ocular toxicity working group, comprising ophthalmologists and oncologists from leading institutions, is developing a consensus grading scale to standardize the evaluation of ADC-induced eye issues.
"As these drugs become more common, we’ll need to work together to navigate these toxicities," he concluded.
Looking ahead
As ADCs continue to transform cancer care, understanding and addressing their ocular implications is essential. The insights shared during this webinar underscore the need for multidisciplinary approaches to ensure patients receive the best possible outcomes—both in oncology and ocular health.
Stay tuned for updates on the ocular toxicity grading scale, expected to be finalized in early 2025, and upcoming webinars that delve deeper into the intersection of eye care and cutting-edge treatments.
Eversight's free webinars are a great way for you to connect, learn and train digitally with leading ophthalmologists and researchers from around the world. We invite you to RSVP for scheduled webinars and browse our recording library.
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About the author
Caithlin Lopes, Senior Director, Business Development
