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Advances in the study of marketed antibody-drug Conjugates (ADCs) for the treatment of breast cancer.

ABSTRACT: Breast cancer continues to have a high incidence rate among female malignancies. Despite significant advancements in treatment modalities, the heterogeneous nature of breast cancer and its resistance to various therapeutic approaches pose considerable challenges. Antibody-drug conjugates (ADCs) effectively merge the specificity of antibodies with the cytotoxicity of chemotherapeutic agents, offering a novel strategy for precision treatment of breast cancer. Notably, trastuzumab emtansine (T-DM1) has provided a new therapeutic option for HER2-positive breast cancer patients globally, especially those resistant to conventional treatments. The development of trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG) has further broadened the applicability of ADCs in breast cancer therapy, presenting new hopes for patients with low HER2 expression and triple-negative breast cancer. However, the application of ADCs presents certain challenges. For instance, their treatment may lead to adverse reactions such as interstitial lung disease, thrombocytopenia, and diarrhea. Moreover, prolonged treatment could result in ADCs resistance, complicating the therapeutic process. Economically, the high costs of ADCs might hinder their accessibility in low-income regions. This article reviews the structure, mechanism of action, and clinical trials of commercially available ADCs for breast cancer treatment, with a focus on the clinical trials of the three drugs, aiming to provide insights for clinical applications and future research.

SUBMITTER: Liang Y

PROVIDER: S-EPMC10862125 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Advances in the study of marketed antibody-drug Conjugates (ADCs) for the treatment of breast cancer.

Liang Yan Y Zhang Purong P Li Feng F Lai Houyun H Qi Tingting T Wang Yixin Y

Frontiers in pharmacology 20240130

Breast cancer continues to have a high incidence rate among female malignancies. Despite significant advancements in treatment modalities, the heterogeneous nature of breast cancer and its resistance to various therapeutic approaches pose considerable challenges. Antibody-drug conjugates (ADCs) effectively merge the specificity of antibodies with the cytotoxicity of chemotherapeutic agents, offering a novel strategy for precision treatment of breast cancer. Notably, trastuzumab emtansine (T-DM1) ...[more]

PMID: 38352694

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Project description:Background and objectiveTriple-negative breast cancer (TNBC) is more aggressive when compared with other breast cancer subtypes, and advanced TNBC (aTNBC) has always been a challenge for clinical treatment. In recent years, significant progress has been made in the research of antibody-drug conjugates (ADCs), especially targeting trophoblast cell-surface antigen 2 (TROP2), as an effective regimen to enhance the potential survival benefit and quality of life of relevant patients. The objective of this narrative review is to provide a comprehensive knowledge on latest progress of ADCs in the treatment of aTNBC. Furthermore, the clinical significance and future research directions for ADCs are also discussed.MethodsAs of December 2023, literature spanning the past decade was comprehensively searched and analyzed across PubMed, Wanfang Data, ClinicalTrials.gov, and relevant academic conferences, to identify the latest published literature or ongoing trials on ADCs for aTNBC. The selected literature primarily focused on the drug structural profile, pharmacological mechanism, important trials targeting different antigens, and other exploratory investigations.Key content and findingsThe advent of precision therapy has been facilitated by the new generation ADCs, which have demonstrated the capacity to prolong survival in patients with refractory aTNBC, and promote the research on molecular biological characteristics of aTNBC. Meanwhile, several clinical issues on treatment are emerging, including a detailed understanding of the clinical profile differences among specific ADCs, identification of the potential indications for ADCs, and management strategies for the adverse effects related to ADCs. Additionally, it is essential to clarify the clinical significance of the expression level of the target antigen for ADCs, to comprehend resistance mechanisms to ADCs, and to determine the optimal sequence of treatments between different ADCs. Furthermore, there is a need to investigate the potential of combination immunotherapy with ADCs. Up to date, the preliminary investigations on the aforementioned issues have been initiated, and further research will facilitate the enhancement of ADCs clinical utilization.ConclusionsThe use of ADCs has been recommended by various clinical guidelines, and significantly altering the landscape of treatment for aTNBC. Nevertheless, further investigation are required to determine the most effective use of ADCs.

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Advances in the study of marketed antibody-drug Conjugates (ADCs) for the treatment of breast cancer.

Publications

Advances in the study of marketed antibody-drug Conjugates (ADCs) for the treatment of breast cancer.

Similar Datasets

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