Affibody-based approaches as potential therapeutics for breast cancer: mechanisms, applications, and future perspectives
4 affiliations
- 1Department of Breast Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
- 2Department of Surgery, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
- 3College of Letters and Sciences, University of California Los Angeles, Los Angeles, CA 90095, USA
- 4Biodesign Center for Bioenergetics, Arizona State University, Tempe, AZ 85287, USA
Abstract
Breast cancer presents a significant therapeutic challenge due to the substantial molecular and genetic diversity among its subtypes, thereby necessitating the development of refined intervention strategies. Macromolecular therapies, such as monoclonal antibodies, are often hindered by suboptimal biodistribution, restricted tumor penetration, and off-target toxicity in advanced diseases. The advent of affibody technology, which utilizes engineered ~7 kilodalton (kDa) scaffold proteins derived from Staphylococcus aureus protein A, introduces a distinct class of targeting agents designed to address several of these limitations. Affibody molecules exhibit favorable biophysical properties, including thermal stability, configurable binding affinities reaching picomolar ranges, rapid systemic clearance, compact molecular size, and modular engineering architecture that enables diverse therapeutic applications. This review explores potential affibody-based therapeutic strategies for breast cancer, with applications targeting human epidermal growth factor receptor 2 (HER2) and human epidermal growth factor receptor 3 (HER3) serving as the most extensively characterized and translationally advanced model systems. Two principal modalities are emphasized: direct receptor antagonism and targeted payload delivery. The latter includes covalent affibody–drug conjugates, cytotoxic fusion proteins, radionuclide-conjugated variants for diagnostic imaging and targeted radionuclide therapy, and affibody-functionalized nano-carriers designed to enhance delivery efficiency. Although most affibody-based therapeutics remain at the preclinical stage, clinical development is most advanced in diagnostic imaging, particularly for HER2-targeted agents that have undergone evaluation in patients. Collectively, this review summarizes the current landscape of affibody-based therapeutic approaches and highlights their translational potential in breast cancer.
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BibTeX
@article{yao2026affibodybased,
title = {{Affibody-based approaches as potential therapeutics for breast cancer: mechanisms, applications, and future perspectives}},
author = {Ru Yao and Keghon Kasparian and Yidong Zhou and Qiang Sun and Armando Giuliano and Bo Pan and Shengxi Chen and Xiaojiang Cui},
journal = {Cell investigation},
year = {2026},
month = oct,
doi = {10.1016/j.clnves.2026.100106},
url = {https://doi.org/10.1016/j.clnves.2026.100106},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Affibody-based approaches as potential therapeutics for breast cancer: mechanisms, applications, and future perspectives
AU - Ru Yao
AU - Keghon Kasparian
AU - Yidong Zhou
AU - Qiang Sun
AU - Armando Giuliano
AU - Bo Pan
AU - Shengxi Chen
AU - Xiaojiang Cui
PY - 2026
DA - 2026/10/07
JO - Cell investigation
DO - 10.1016/j.clnves.2026.100106
UR - https://doi.org/10.1016/j.clnves.2026.100106
AB - Breast cancer presents a significant therapeutic challenge due to the substantial molecular and genetic diversity among its subtypes, thereby necessitating the development of refined intervention strategies. Macromolecular therapies, such as monoclonal antibodies, are often hindered by suboptimal biodistribution, restricted tumor penetration, and off-target toxicity in advanced diseases. The advent of affibody technology, which utilizes engineered ~7 kilodalton (kDa) scaffold proteins derived from Staphylococcus aureus protein A, introduces a distinct class of targeting agents designed to address several of these limitations. Affibody molecules exhibit favorable biophysical properties, including thermal stability, configurable binding affinities reaching picomolar ranges, rapid systemic clearance, compact molecular size, and modular engineering architecture that enables diverse therapeutic applications. This review explores potential affibody-based therapeutic strategies for breast cancer, with applications targeting human epidermal growth factor receptor 2 (HER2) and human epidermal growth factor receptor 3 (HER3) serving as the most extensively characterized and translationally advanced model systems. Two principal modalities are emphasized: direct receptor antagonism and targeted payload delivery. The latter includes covalent affibody–drug conjugates, cytotoxic fusion proteins, radionuclide-conjugated variants for diagnostic imaging and targeted radionuclide therapy, and affibody-functionalized nano-carriers designed to enhance delivery efficiency. Although most affibody-based therapeutics remain at the preclinical stage, clinical development is most advanced in diagnostic imaging, particularly for HER2-targeted agents that have undergone evaluation in patients. Collectively, this review summarizes the current landscape of affibody-based therapeutic approaches and highlights their translational potential in breast cancer.
SN - 3050-5380
ER -