Next-generation antibody-drug conjugates for breast cancer: Moving beyond HER2 and TROP2

Ilana Schlam; Ruth Moges; Stefania Morganti; Sara M Tolaney; Paolo Tarantino

doi:10.1016/j.critrevonc.2023.104090

Next-generation antibody-drug conjugates for breast cancer: Moving beyond HER2 and TROP2

Crit Rev Oncol Hematol. 2023 Oct:190:104090. doi: 10.1016/j.critrevonc.2023.104090. Epub 2023 Aug 9.

Authors

Ilana Schlam¹, Ruth Moges², Stefania Morganti³, Sara M Tolaney⁴, Paolo Tarantino⁵

Affiliations

¹ Department of Hematology and Oncology, Tufts Medical Center, Boston, MA, USA.
² Department of Internal Medicine, Brigham and Women's Hospital, Boston, MA, USA.
³ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Division of New Drugs and Early Drug Development, European Institute of Oncology IRCCS, Milan, Italy; Department of Oncology and Onco-Hematology, University of Milan, Milan, Italy; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁴ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
⁵ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Division of New Drugs and Early Drug Development, European Institute of Oncology IRCCS, Milan, Italy; Department of Oncology and Onco-Hematology, University of Milan, Milan, Italy. Electronic address: paolo_tarantino@dfci.harvard.edu.

PMID: 37562695
DOI: 10.1016/j.critrevonc.2023.104090

Abstract

Antibody-drug conjugates (ADCs) have reshaped the treatment of several malignancies, including breast cancer. Two ADCs are currently approved for the treatment of each breast cancer subtype, including the HER2 targeted ADCs trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd), and the TROP2-targeted ADC sacituzumab govitecan. Each of the ADC components (antibody, linker, and payload) plays a key role in determining the efficacy and toxicity profile of an individual ADC, and their modification can lead to major changes in the clinical profile of these agents. Leveraging the knowledge from three decades of development in the field, several novel ADCs are currently being investigated. Some approaches include targeting different antigens beyond the established HER2/TROP2, or evaluating innovative constructs, such as bispecific ADCs, ADCs with dual payload, immune-modulating ADCs, radionuclide drug conjugates, and masked ADCs, among others. In this review article we discuss the evolving landscape of novel ADCs, highlighting opportunities and challenges emerging in the field.

Keywords: Antibody-drug conjugates; Breast cancer; Drug development; Targeted therapies.

Publication types

Review

MeSH terms

Ado-Trastuzumab Emtansine / therapeutic use
Antineoplastic Agents* / therapeutic use
Breast Neoplasms* / drug therapy
Female
Humans
Immunoconjugates* / therapeutic use

Substances

Ado-Trastuzumab Emtansine
Immunoconjugates
Antineoplastic Agents