Driven by increasingly mature technologies, ADC payloads have undergone three generations of innovation. In the first generation of ADC drugs, traditional chemotherapy agents such as methotrexate, vincristine, and doxorubicin were used as cytotoxic payloads. However, due to the insufficient cytotoxicity of these first-generation ADCs against cancer cells, lack of tumor selectivity, and limited accumulation in target cells, their efficacy was even inferior to their parent drugs, leading to clinical failures. Most second-generation ADCs utilized significantly more effective microtubule inhibitors as payloads. Unfortunately, although microtubule inhibitors are highly effective against actively dividing tumor cells, they are less effective against quiescent cancer cells. To overcome this limitation, there has been a shift towards using DNA-damaging agents capable of targeting the entire cell cycle, including topoisomerase I inhibitors, as the cytotoxic payloads of most third-generation ADCs.
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"Over about ten years my body slowly changed. As a youth I was involved with the Great British training programmes for swimming and rowing and I could eat whatever I wanted. Since I retired from competition, what was muscle turned to fat and I lost my drive to train.
"Over about ten years my body slowly changed. As a youth I was involved with the Great British training programmes for swimming and rowing and I could eat whatever I wanted. Since I retired from competition, what was muscle turned to fat and I lost my drive to train.
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