Generation of antibody‐drug conjugate resistant models

© 2021 by the authors.In the last 20 years, antibody-drug conjugates (ADCs) have been incorporated into the oncology clinic as treatments for several types of cancer. So far, the Food and Drug Administration (FDA) has approved 11 ADCs and other ADCs are in the late stages of clinical development. Despite the efficacy of this type of drug, the tumors of some patients may result in resistance to ADCs. Due to this, it is essential not only to comprehend resistance mechanisms but also to develop strategies to overcome resistance to ADCs. To reach these goals, the generation and use of preclinical models to study those mechanisms of resistance are critical. Some cells or patient tumors may result in primary resistance to the action of an ADC, even if they express the antigen against which the ADC is directed. Isolated primary tumoral cells, cell lines, or patient explants (patient-derived xenografts) with these characteristics can be used to study primary resistance. The most common method to generate models of secondary resistance is to treat cancer cell lines or tumors with an ADC. Two strategies, either continuous treatment with the ADC or intermittent treatment, have successfully been used to develop those resistance models.AP: Ministry of Economy and Competitiveness of Spain (BFU2015-71371-R), the Instituto de Salud Carlos III through CIBERONC, Junta de Castilla y León (CSI146P20), ALMOM, ACMUMA, UCCTA and the CRIS Cancer Foundation. AO: Instituto de Salud Carlos III (PI19/00808), ACEPAIN, and CRIS Cancer Foundation. Work carried out in AP and AO laboratories receives support from the European Community through the Regional Development Funding Program (FEDER). LGS was recipient of a predoctoral contract (BES-2016-077748); and is at present contracted by the Cancer Research Foundation of the Salamanca University (FICUS)