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Shedding light on triple-negative breast cancer with Trop2-targeted antibody-drug conjugates.

ABSTRACT: Triple-negative breast cancer (TNBC) is well-known as the most aggressive subtype of breast cancer. Because TNBC does not express Her2, estrogen receptor, and progesterone receptors, there had been no effective U.S. Food and Drug Administration-approved targeted therapy for it until PARP inhibitors and two PD-1/PD-L1 monoclonal antibodies were approved for treatment of TNBC. Most recently, an antibody-drug conjugate (ADC), called sacituzumab govitecan (SG), was approved for the treatment of TNBC patients previously received chemotherapy with advanced disease. SG consists of an anti-trophoblast cell-surface antigen 2 (Trop2) antibody conjugated with a topoisomerase I inhibitor, SN-38, which is diffused out of the targeted Trop2 positive cancer cells and induces the bystander killing effect on surrounding cells regardless of their Trop2 expression status. In the Phase III clinical trial, TNBC patients treated with SG showed significantly longer progression-free and overall survival compared to those who were received chemotherapy. In the present review, we summarized the cellular function and signaling of Trop2, the mechanism of action of SG, and the clinical trials of SG that led to its quick approval for TNBC. In addition, we introduced the current ongoing clinical trials of SG as well as another Trop2 ADC, which has potential to overcome some disadvantages of SG.

SUBMITTER: Jabbarzadeh Kaboli P

PROVIDER: S-EPMC9077081 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Shedding light on triple-negative breast cancer with Trop2-targeted antibody-drug conjugates.

Jabbarzadeh Kaboli Parham P Shabani Shima S Sharma Sagar S Partovi Nasr Minoo M Yamaguchi Hirohito H Hung Mien-Chie MC

American journal of cancer research 20220415 4

Triple-negative breast cancer (TNBC) is well-known as the most aggressive subtype of breast cancer. Because TNBC does not express Her2, estrogen receptor, and progesterone receptors, there had been no effective U.S. Food and Drug Administration-approved targeted therapy for it until PARP inhibitors and two PD-1/PD-L1 monoclonal antibodies were approved for treatment of TNBC. Most recently, an antibody-drug conjugate (ADC), called sacituzumab govitecan (SG), was approved for the treatment of TNBC ...[more]

PMID: 35530278

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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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Shedding light on triple-negative breast cancer with Trop2-targeted antibody-drug conjugates.

Publications

Shedding light on triple-negative breast cancer with Trop2-targeted antibody-drug conjugates.

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