Article
Michael Z. Liao, Dan Lu, Matts KĂĽgedal, Dale Miles, Divya Samineni, Stephanie N. Liu, Chunze Li
Rise of Antibody-Drug Conjugates: The Present and Future
Summary
- Antibody-drug conjugates (ADCs) are designed for targeted cancer therapy by delivering cytotoxic agents specifically to tumor cells, minimizing harm to normal cells.
- ADCs have evolved significantly since the first FDA approval in 2000, with advancements leading to approvals for various tumor types.
- In breast cancer treatment, ADCs have become standard for HER2+, HR+, and triple-negative subtypes.
- ADCs can now target tumors with low or heterogeneous antigen expression and are effective even without specific target expression in some cases.
- These therapies, while targeted, can still cause toxicities, necessitating careful patient selection and monitoring.
- Resistance mechanisms must be studied to optimize ADC sequencing in treatment plans.
- Future ADC developments may include using immune-stimulating agents or combining them with immunotherapy and other targeted treatments to enhance efficacy in treating solid tumors.
Antibody-drug conjugates (ADCs) are a rapidly emerging class of therapeutic agents that combine the target specificity of a monoclonal antibody (mAb) with the lethality of cytotoxic cellular poison. With ongoing advancements in drug engineering and fresh biologic insight into mechanisms of drug action, the ADC field is still early in its evolution. Despite this, there are over a 100 new ADCs in clinical trials encompassing a wide variety of tumor types. This explosion of interest is, in part, due to the spectacular success in the past 5 years, particularly in some highly treatment-refractory diseases. This review will provide a brief overview on ADC design and mechanism of action, highlighting ADCs currently in use for breast and urothelial cancer (UC) where some of the most significant clinical advancements have been achieved. The toxicity profile of these agents, development of resistance, and the potential of combination therapies with ADCs will be explored.
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