New era for emerging therapeutic targeting human epidermal growth factor receptor 3 (HER 3) in advanced nonsmall cell lung cancer and metastatic breast cancer
Abstract Human epidermal growth factor receptor 3 (HER3) is a member of the transmembrane receptor tyrosine kinase family. Upregulation of HER3 pathway has been implicated as a mechanism of resistance in solid tumors, particularly in estrogen receptor positive, HER2 positive breast cancer and epider...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-09-01
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| Series: | MedComm – Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/mog2.19 |
| _version_ | 1797829242806861824 |
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| author | Yasar Ahmed Thamir Mahgoub Maha Al Sindi José J. Berenguer‐Pina |
| author_facet | Yasar Ahmed Thamir Mahgoub Maha Al Sindi José J. Berenguer‐Pina |
| author_sort | Yasar Ahmed |
| collection | DOAJ |
| description | Abstract Human epidermal growth factor receptor 3 (HER3) is a member of the transmembrane receptor tyrosine kinase family. Upregulation of HER3 pathway has been implicated as a mechanism of resistance in solid tumors, particularly in estrogen receptor positive, HER2 positive breast cancer and epidermal growth factor (EGFR) mutant nonsmall cell lung cancer. Several studies suggest that HER3 overexpression represents a negative prognostic biomarker associated with poor survival. Preclinical and clinical studies of anti‐HER3 investigational therapies suggest that expression of the HER3 ligand, neuregulin, may predict response to treatment. Despite its emergence as a key cancer therapeutic target, HER3 cannot be targeted with traditional tyrosine kinase inhibitors therapy due to its weak kinase activity. Monoclonal and bispecific antibodies targeting HER3 have been developed and tested in early phase trials. Objective responses were limited when first‐generation HER3‐specific monoclonal antibodies were investigated as monotherapies in phase 1 and 2 clinical trials for nonsmall cell lung cancer (NSCLC) and metastatic breast cancer (MBC). MBC and NSCLC HER3 specific antibody‐drug conjugates have shown encouraging results in resistance in cancer cells, particularly in those that overexpress HER3. These agents have shown some promise in early phase trials in both NSCLC and MBC setting in heavily pretreated patients with varying degrees of response. It is unclear which subgroup of patients will truly benefit from targeting HER3 as these therapies are under investigation. |
| first_indexed | 2024-04-09T13:17:19Z |
| format | Article |
| id | doaj.art-f9da62498af849d4927890b7ee5c5256 |
| institution | Directory Open Access Journal |
| issn | 2769-6448 |
| language | English |
| last_indexed | 2024-04-09T13:17:19Z |
| publishDate | 2022-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | MedComm – Oncology |
| spelling | doaj.art-f9da62498af849d4927890b7ee5c52562023-05-11T17:25:27ZengWileyMedComm – Oncology2769-64482022-09-0112n/an/a10.1002/mog2.19New era for emerging therapeutic targeting human epidermal growth factor receptor 3 (HER 3) in advanced nonsmall cell lung cancer and metastatic breast cancerYasar Ahmed0Thamir Mahgoub1Maha Al Sindi2José J. Berenguer‐Pina3Medical Oncology Department St Vincent's University Hospital Dublin IrelandMedical Oncology Department, Mid‐Western Cancer Centre University Hospital Limerick Limerick IrelandMedical Oncology Department St Vincent's University Hospital Dublin IrelandMedical Oncology Department St Vincent's University Hospital Dublin IrelandAbstract Human epidermal growth factor receptor 3 (HER3) is a member of the transmembrane receptor tyrosine kinase family. Upregulation of HER3 pathway has been implicated as a mechanism of resistance in solid tumors, particularly in estrogen receptor positive, HER2 positive breast cancer and epidermal growth factor (EGFR) mutant nonsmall cell lung cancer. Several studies suggest that HER3 overexpression represents a negative prognostic biomarker associated with poor survival. Preclinical and clinical studies of anti‐HER3 investigational therapies suggest that expression of the HER3 ligand, neuregulin, may predict response to treatment. Despite its emergence as a key cancer therapeutic target, HER3 cannot be targeted with traditional tyrosine kinase inhibitors therapy due to its weak kinase activity. Monoclonal and bispecific antibodies targeting HER3 have been developed and tested in early phase trials. Objective responses were limited when first‐generation HER3‐specific monoclonal antibodies were investigated as monotherapies in phase 1 and 2 clinical trials for nonsmall cell lung cancer (NSCLC) and metastatic breast cancer (MBC). MBC and NSCLC HER3 specific antibody‐drug conjugates have shown encouraging results in resistance in cancer cells, particularly in those that overexpress HER3. These agents have shown some promise in early phase trials in both NSCLC and MBC setting in heavily pretreated patients with varying degrees of response. It is unclear which subgroup of patients will truly benefit from targeting HER3 as these therapies are under investigation.https://doi.org/10.1002/mog2.19HER3metastatic breast cancerNSCLC |
| spellingShingle | Yasar Ahmed Thamir Mahgoub Maha Al Sindi José J. Berenguer‐Pina New era for emerging therapeutic targeting human epidermal growth factor receptor 3 (HER 3) in advanced nonsmall cell lung cancer and metastatic breast cancer MedComm – Oncology HER3 metastatic breast cancer NSCLC |
| title | New era for emerging therapeutic targeting human epidermal growth factor receptor 3 (HER 3) in advanced nonsmall cell lung cancer and metastatic breast cancer |
| title_full | New era for emerging therapeutic targeting human epidermal growth factor receptor 3 (HER 3) in advanced nonsmall cell lung cancer and metastatic breast cancer |
| title_fullStr | New era for emerging therapeutic targeting human epidermal growth factor receptor 3 (HER 3) in advanced nonsmall cell lung cancer and metastatic breast cancer |
| title_full_unstemmed | New era for emerging therapeutic targeting human epidermal growth factor receptor 3 (HER 3) in advanced nonsmall cell lung cancer and metastatic breast cancer |
| title_short | New era for emerging therapeutic targeting human epidermal growth factor receptor 3 (HER 3) in advanced nonsmall cell lung cancer and metastatic breast cancer |
| title_sort | new era for emerging therapeutic targeting human epidermal growth factor receptor 3 her 3 in advanced nonsmall cell lung cancer and metastatic breast cancer |
| topic | HER3 metastatic breast cancer NSCLC |
| url | https://doi.org/10.1002/mog2.19 |
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