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Antibody-drug conjugates (ADCs) are one of the fastest-growing anti-cancer drugs. This approach comprises a monoclonal antibody conjugated to the cytotoxic payload via a chemical linker that directed towards a target antigen expressed on the cancer cell surface, reducing systemic exposure and therefore toxicity. ADCs are complex molecules that require careful attention to various components. Selection of an appropriate target, a monoclonal antibody, cytotoxic payload, and the manner in which the antibody is linked to the payload are key determinants of the safety and efficacy of ADCs. This review provides an overview of the systemic evaluation of each component of an ADC design, improved understanding of the mechanism of action of ADC and mechanistic pathways involved in ADC resistance and various strategies to optimize ADC design. Moreover, this review also shed light on the current status of ADCs that have gained regulatory approval from the US Food and Drug Administration (FDA) including a description of biology and chemistry, metabolic profiles, adverse events, drug interactions, and the future perspective on combination strategies with other agents, including immunotherapy. Received June 2, August 22, 22, 2019. Copyright ©2019, Log in using your username and password Username * Forgot your user name or password? Purchase access You may purchase access to this article. This will require you to create an account if you don't.