T-DM1 with concurrent radiotherapy in HER2-positive breast cancer: preclinical evaluation and mechanisms, prediction, and exploration of adverse effects
Abstract Human epidermal growth factor receptor 2 (HER-2) serves as a pivotal target for breast cancer treatment and a vital prognostic marker. Anti-HER-2 therapies, which are integral to the management of HER-2-positive breast cancer, including monoclonal antibodies (e.g., trastuzumab and pertuzuma...
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| Language: | English |
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Springer
2025-05-01
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| Series: | Discover Oncology |
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| Online Access: | https://doi.org/10.1007/s12672-025-02239-2 |
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| author | Guangmin Wan Lu Yang Quan Wang Gang Xu |
| author_facet | Guangmin Wan Lu Yang Quan Wang Gang Xu |
| author_sort | Guangmin Wan |
| collection | DOAJ |
| description | Abstract Human epidermal growth factor receptor 2 (HER-2) serves as a pivotal target for breast cancer treatment and a vital prognostic marker. Anti-HER-2 therapies, which are integral to the management of HER-2-positive breast cancer, including monoclonal antibodies (e.g., trastuzumab and pertuzumab), tyrosine kinase inhibitors (e.g., lapatinib and pyrotinib), and antibody–drug conjugates (ADCs) such as trastuzumab emtansine (T-DM1). ADCs consist of a monoclonal antibody, a linker, and a cytotoxic payload, engineered to deliver chemotherapy selectively to tumor cells, thereby reducing the systemic toxicity associated with traditional chemotherapy. T-DM1, a HER-2-targeting ADC, combines the humanized anti-HER-2 IgG1 trastuzumab with DM1, a cytotoxic agent that inhibits microtubule formation. T-DM1 has significantly enhanced the prognosis of HER-2-positive breast cancer patients who fail to achieve a pathological complete response or develop distant metastases after neoadjuvant trastuzumab and pertuzumab therapy. While the combination therapy of T-DM1 with radiotherapy demonstrates an acceptable safety profile overall, clinicians should remain vigilant regarding potential severe treatment-related toxicities that have been observed in specific clinical scenarios. Nevertheless, limited research exists regarding the adverse effects and mechanisms of T-DM1 in combination with radiotherapy. This review investigates preclinical studies on the interactions between T-DM1 and radiotherapy, investigates associated adverse effects and their underlying mechanisms, identifies predictive factors and prognostic implications, and explores potential therapeutic strategies involving the concurrent T-DM1 with radiotherapy. |
| format | Article |
| id | doaj-art-0acccd0f9bab4deaa56f10283a004ff7 |
| institution | Kabale University |
| issn | 2730-6011 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj-art-0acccd0f9bab4deaa56f10283a004ff72025-08-20T03:48:18ZengSpringerDiscover Oncology2730-60112025-05-0116111410.1007/s12672-025-02239-2T-DM1 with concurrent radiotherapy in HER2-positive breast cancer: preclinical evaluation and mechanisms, prediction, and exploration of adverse effectsGuangmin Wan0Lu Yang1Quan Wang2Gang Xu3Department of Radiation Oncology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer HospitalDepartment of Radiation Oncology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer HospitalDepartment of Radiation Oncology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer HospitalDepartment of Radiation Oncology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer HospitalAbstract Human epidermal growth factor receptor 2 (HER-2) serves as a pivotal target for breast cancer treatment and a vital prognostic marker. Anti-HER-2 therapies, which are integral to the management of HER-2-positive breast cancer, including monoclonal antibodies (e.g., trastuzumab and pertuzumab), tyrosine kinase inhibitors (e.g., lapatinib and pyrotinib), and antibody–drug conjugates (ADCs) such as trastuzumab emtansine (T-DM1). ADCs consist of a monoclonal antibody, a linker, and a cytotoxic payload, engineered to deliver chemotherapy selectively to tumor cells, thereby reducing the systemic toxicity associated with traditional chemotherapy. T-DM1, a HER-2-targeting ADC, combines the humanized anti-HER-2 IgG1 trastuzumab with DM1, a cytotoxic agent that inhibits microtubule formation. T-DM1 has significantly enhanced the prognosis of HER-2-positive breast cancer patients who fail to achieve a pathological complete response or develop distant metastases after neoadjuvant trastuzumab and pertuzumab therapy. While the combination therapy of T-DM1 with radiotherapy demonstrates an acceptable safety profile overall, clinicians should remain vigilant regarding potential severe treatment-related toxicities that have been observed in specific clinical scenarios. Nevertheless, limited research exists regarding the adverse effects and mechanisms of T-DM1 in combination with radiotherapy. This review investigates preclinical studies on the interactions between T-DM1 and radiotherapy, investigates associated adverse effects and their underlying mechanisms, identifies predictive factors and prognostic implications, and explores potential therapeutic strategies involving the concurrent T-DM1 with radiotherapy.https://doi.org/10.1007/s12672-025-02239-2T-DM1RadiotherapyHER-2ADCsAdverse effects |
| spellingShingle | Guangmin Wan Lu Yang Quan Wang Gang Xu T-DM1 with concurrent radiotherapy in HER2-positive breast cancer: preclinical evaluation and mechanisms, prediction, and exploration of adverse effects Discover Oncology T-DM1 Radiotherapy HER-2 ADCs Adverse effects |
| title | T-DM1 with concurrent radiotherapy in HER2-positive breast cancer: preclinical evaluation and mechanisms, prediction, and exploration of adverse effects |
| title_full | T-DM1 with concurrent radiotherapy in HER2-positive breast cancer: preclinical evaluation and mechanisms, prediction, and exploration of adverse effects |
| title_fullStr | T-DM1 with concurrent radiotherapy in HER2-positive breast cancer: preclinical evaluation and mechanisms, prediction, and exploration of adverse effects |
| title_full_unstemmed | T-DM1 with concurrent radiotherapy in HER2-positive breast cancer: preclinical evaluation and mechanisms, prediction, and exploration of adverse effects |
| title_short | T-DM1 with concurrent radiotherapy in HER2-positive breast cancer: preclinical evaluation and mechanisms, prediction, and exploration of adverse effects |
| title_sort | t dm1 with concurrent radiotherapy in her2 positive breast cancer preclinical evaluation and mechanisms prediction and exploration of adverse effects |
| topic | T-DM1 Radiotherapy HER-2 ADCs Adverse effects |
| url | https://doi.org/10.1007/s12672-025-02239-2 |
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