Reducing resistance of cancer cells to ADC payloads: Biomarker discovery & approaches to tackle drug resistance
28 Apr 2026
ADC Cytotoxic Payload
- What cellular pathways are responsible for the altered intracellular trafficking or limited lysosomal release of ADC payloads, and how do these contribute to acquired resistance in tumor cells?
- How do genetic or epigenetic changes in tumor cells influence the expression or activity of efflux transporters responsible for pump-out of ADC payloads, and what strategies can mitigate this resistance pathway?
- What metabolic or enzymatic adaptations within tumor cells affect the activation, detoxification, or degradation of specific ADC payloads, leading to resistance, and how can payload design be optimized to evade these processes?
- How does the tumor microenvironment—such as hypoxia, acidosis, or immune cell infiltration—modulate the sensitivity of cancer cells to ADC payloads and drive resistance, and what combination strategies could enhance payload potency?
- Can rational design of novel payloads or linker chemistries generate ADCs capable of circumventing established resistance mechanisms to existing cytotoxics, and what preclinical models best predict such innovations’ therapeutic advantages?
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