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Review
. 2025 Dec 17:17:17588359251396656.
doi: 10.1177/17588359251396656. eCollection 2025.

Current landscape of sequencing ADCs in metastatic breast cancer

Shannon McLaughlin  1 , Lis V Ravani  1 , Beverly Moy  1 , Arielle J Medford  1 , Steven J Isakoff  1 , Ting Liu  1 , Leif W Ellisen  1 , Laura M Spring  1 , Seth A Wander  1 , Rachel O Abelman  2
Affiliations
Review

Current landscape of sequencing ADCs in metastatic breast cancer

Shannon McLaughlin et al. Ther Adv Med Oncol. .

Abstract

Antibody-drug conjugates (ADCs) have revolutionized the care of advanced breast cancer. ADCs pair an antibody targeted against a tumor-associated antigen with a cytotoxic payload, aiming to deliver therapy more effectively and with fewer off-target toxicities. Given the growth of ADCs in the past few years, patients are now candidates for multiple agents sequentially. Optimal strategies for sequencing ADCs are not yet known. Here we review retrospective data on ADC sequencing, translational understanding of mechanisms of resistance, and novel ADCs and combination agents in the pipeline that aim to improve upon currently available care.

Keywords: antibody-drug conjugates; breast cancer; drug resistance; metastasis; targeted therapy; translational research; treatment sequencing.

Plain language summary

Current understanding of sequencing antibody-drug conjugates (ADCs) Antibody-drug conjugates (ADCs) are a new kind of cancer treatment that have made a big difference for people with breast cancer. What they do is combine a chemotherapy drug with an antibody that seeks out cancer cells. Because the antibody guides the chemo directly to the tumor, ADCs can kill cancer cells more effectively and cause fewer side effects than ordinary chemotherapy. However, doctors do not yet know the best order or timing for giving different ADCs one after the other. In this article, the authors review what patient studies tell us so far about sequencing ADCs, and also look at lab studies that explore how cancer cells become resistant. Finally, they talk about promising new ADCs in development.

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Conflict of interest statement

R.O.A. has served as an advisor/consultant for Medspoke and MD Outlook. S.A.W. has served as an advisory/consultant for Foundation Medicine, Veracyte, Hologic, Eli Lilly, Biovica, Pfizer/Arvinas, Puma Biotechnology, Novartis, AstraZeneca, Genentech, Regor Therapeutics, Stemline/Menarini, Gilead. S.A.W. has provided educational speaking for Eli Lilly, Guardant Health, 2ndMD. S.A.W. reports institutional research support from Genentech, Eli Lilly, Pfizer/Arvinas, Nuvation Bio, Regor Therapeutics, Sermonix, Puma Biotechnology, Stemline/Menarini, Phoenix Molecular Designs. L.W.E. has served as advisor/consultant to Gilead, Astra Zeneca, Kisoji, and Atavistik. L.W.E. receives research funding from Sanofi and Eisai.

References

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