RE:RE:RE:ADCs - excess toxicities & unfavorable risk-benefit profilesThe Limitations of Complexity
Despite their success in clinical trials, ADCs are not a magic bullet. The main drawback is that tumors develop resistance to them over time. Toxicity is also a concern, especially as cytotoxic payloads become more and more potent.
“The clinical pharmacology of ADCs highly complex,” said William D. Figg, an oncologist at the National Institutes of Health. “Given that payloads are cytotoxic, a relatively small increase in the systemic exposure of the payload can cause significant side effects.” Understanding the drug’s pharmacology to optimize the dose is crucial from a safety perspective, he added. Although ADCs can be combined with other therapies such as chemotherapy, they can sometimes have adverse drug interactions with other cancer treatments.
To optimize ADC therapy, Figg said researchers will have to understand and overcome the development of resistance, design more-stable linkers and identify more-specific therapeutic targets. But, he added, perhaps improved ADC technology will usher in an era of precision medicine.