Alteration of Trop-2 expression in breast cancer cells by clinically used therapeutic agents and acquired tamoxifen resistance

Zhu, Jing; Wu, Wenwen; Togashi, Yukiko; Nihira, Naoe Taira; Johmura, Yoshikazu; Zhu, Dajiang; Nakanishi, Makoto; Miyoshi, Yasuo; Ohta, Tomohiko

doi:10.1007/s12282-022-01389-3

Cited by 11 publications

(8 citation statements)

References 36 publications

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“…The two known resistance mechanisms are AKT activation and Notch signaling. A third possible mechanism seems to be tamoxifen-induced Trop-2 expression through the transcription factor TFEB [ 56 ]. There are probably also other mechanisms that are not yet known.…”

Section: Discussionmentioning

confidence: 99%

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The Relationship between Trop-2, Chemotherapeutic Drugs, and Chemoresistance

Koltai,

Fliegel

2023

IJMS

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Trop-2 is a highly conserved one-pass transmembrane mammalian glycoprotein that is normally expressed in tissues such as the lung, intestines, and kidney during embryonic development. It is overexpressed in many epithelial cancers but is absent in non-epithelial tumors. Trop-2 is an intracellular calcium signal transducer that participates in the promotion of cell proliferation, migration, invasion, metastasis, and probably stemness. It also has some tumor suppressor effects. The pro-tumoral actions have been thoroughly investigated and reported. However, Trop-2’s activity in chemoresistance is less well known. We review a possible relationship between Trop-2, chemotherapy, and chemoresistance. We conclude that there is a clear role for Trop-2 in some specific chemoresistance events. On the other hand, there is no clear evidence for its participation in multidrug resistance through direct drug transport. The development of antibody conjugate drugs (ACD) centered on anti-Trop-2 monoclonal antibodies opened the gates for the treatment of some tumors resistant to classic chemotherapies. Advanced urothelial tumors and breast cancer were among the first malignancies for which these ACDs have been employed. However, there is a wide group of other tumors that may benefit from anti-Trop-2 therapy as soon as clinical trials are completed.

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Section: Discussionmentioning

confidence: 99%

“…Furthermore, chemotherapy can, in some cases, increase Trop-2 expression. For example, tamoxifen treatment significantly increased Trop-2 expression in breast luminal cancer cell lines [ 56 ].…”

Section: Trop-2 and Drug Resistancementioning

confidence: 99%

The Relationship between Trop-2, Chemotherapeutic Drugs, and Chemoresistance

Koltai,

Fliegel

2023

IJMS

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“…It has also been shown that patients with lower TROP-2 expression have reduced mPFS when treated with sacituzumab govitecan as compared to those with higher expression (2.7 months vs. 6.9 months, respectively) [ 55 ]. Zhu et al, 2022, evaluated how various treatments could alter TROP-2 expression and found that treatment with tamoxifen significantly increased TROP-2 expression [ 56 ].…”

Section: Challenges and Resistance Mechanismsmentioning

confidence: 99%

Antibody–Drug Conjugates in Breast Cancer: Current Status and Future Directions

Mark,

Lee,

Cui

et al. 2023

IJMS

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Antibody drug conjugates (ADCs) are novel medications that combine monoclonal antibodies with cytotoxic payloads, enabling the selective delivery of potent drugs to cancer cells expressing specific surface antigens. This targeted strategy seeks to optimize treatment effectiveness while reducing the risk of systemic toxicity, distinguishing ADCs from conventional chemotherapy. The rapid growth in ADC research has led to numerous developments and approvals for cancer treatment, with significant impacts on the management of breast cancer. ADCs like T-DXd for HER2-low disease and sacituzumab govitecan for triple negative breast cancer (TNBC) have provided valuable options for challenging subtypes of breast cancer. However, essential questions still need to be addressed, including the optimal order of ADCs amidst the growing number of newly developed ones and strategies to overcome resistance mechanisms. Preclinical studies have shed light on potential resistance mechanisms, emphasizing the potential benefit of combinational approaches with other agents such as immune checkpoint inhibitors (ICIs) and targeted tyrosine kinase inhibitors (TKIs) to enhance treatment effectiveness. Additionally, personalized approaches based on molecular profiling hold promise in tailoring ADC treatments to individual tumors, identifying unique molecular markers for each patient to optimize treatment efficacy while minimizing side effects.

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“…Trophoblast cell surface antigen 2 (Trop2) is a widely expressed glycoprotein and a member of the epithelial cell adhesion molecule (EpCAM) family in many normal tissues, and overexpressed in a variety of human cancers, including gastric cancer [ 98 ] and breast cancer [ 99 ]. Trop2 has potential in promoting epithelial-mesenchymal transition (EMT) in human breast cancer [ 100 ].…”

Section: Car T-cell Therapy In Solid Tumorsmentioning

confidence: 99%

Efficacy, Safety, and Challenges of CAR T-Cells in the Treatment of Solid Tumors

Chen

Lü

2022

Cancers

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Immunotherapy has been the fifth pillar of cancer treatment in the past decade. Chimeric antigen receptor (CAR) T-cell therapy is a newly designed adoptive immunotherapy that is able to target and further eliminate cancer cells by engaging with MHC-independent tumor-antigens. CAR T-cell therapy has exhibited conspicuous clinical efficacy in hematological malignancies, but more than half of patients will relapse. Of note, the efficacy of CAR T-cell therapy has been even more disappointing in solid tumors. These challenges mainly include (1) the failures of CAR T-cells to treat highly heterogeneous solid tumors due to the difficulty in identifying unique tumor antigen targets, (2) the expression of target antigens in non-cancer cells, (3) the inability of CAR T-cells to effectively infiltrate solid tumors, (4) the short lifespan and lack of persistence of CAR T-cells, and (5) cytokine release syndrome and neurotoxicity. In combination with these characteristics, the ideal CAR T-cell therapy for solid tumors should maintain adequate T-cell response over a long term while sparing healthy tissues. This article reviewed the status, clinical application, efficacy, safety, and challenges of CAR T-cell therapies, as well as the latest progress of CAR T-cell therapies for solid tumors. In addition, the potential strategies to improve the efficacy of CAR T-cells and prevent side effects in solid tumors were also explored.

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Alteration of Trop-2 expression in breast cancer cells by clinically used therapeutic agents and acquired tamoxifen resistance

Cited by 11 publications

References 36 publications

The Relationship between Trop-2, Chemotherapeutic Drugs, and Chemoresistance

The Relationship between Trop-2, Chemotherapeutic Drugs, and Chemoresistance

Antibody–Drug Conjugates in Breast Cancer: Current Status and Future Directions

Efficacy, Safety, and Challenges of CAR T-Cells in the Treatment of Solid Tumors

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