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Weiterempfehlung
Marcel Rieker
Targeted Combination Therapy: Discovery and Evaluation of Synergistic Anticancer Effects of Anti-HER2-Duocarmycin Antibody-Drug Conjugates Combined with ATR Inhibitors
While the global cancer burden is still high with 10 million people being diagnosed with cancer and 6 million cancer-related deaths yearly, academia and industry are developing more and more sophisticated therapies to combat cancer. One recent development are antibody-drug conjugates (ADCs) which consist of an antibody portion that mediates tumor selectivity and a highly cytotoxic drug designed to efficiently kill cancer cells. The majority of ADCs in clinical trials today carries payloads targeting the cytoskeleton. However, microtubule-targeting agents often lack clinical efficacy and thus, drugs with other mode of actions are in focus of current ADC research. With Mylotarg and Besponsa for example two ADCs carrying DNA damaging agents are already approved and SYD985 an ADC carrying the DNA-alkylating agent duocarmycin is currently showing promising results in a clinical phase III study. Although ADCs have shown promising anticancer effects and often come along with a broadened therapeutic window compared to conventional chemotherapy, there is still room for improvement regarding e.g. saftey aspects. Establishment of combination therapy for ADCs might pose a strategy for increasing efficacy, diminish side-effects and slow down resistance development especially because single agent therapy has seldom been curative. This work aimed at the discovery of a synergistic drug combination that might enhance the efficacy of duocarmycin-based ADCs like the clinically evaluated ADC SYD985.
Schlagwörter: antibody-drug conjugates; combination therapy; ATR; ATR inhibitors; cancer; cancer therapy; cancer cells
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