Targeting c-Met in breast cancer: From mechanisms of chemoresistance to novel therapeutic strategies
Breast cancer presents a significant challenge due to its heterogeneity and propensity for developing chemoresistance, particularly in the triple-negative subtype. c-Mesenchymal epithelial transition factor (c-Met), a receptor tyrosine kinase, presents a promising target for breast cancer therapy du...
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Elsevier
2024-01-01
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| Series: | Current Research in Pharmacology and Drug Discovery |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590257124000312 |
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| author | Emeka Eze Joshua Iweala Doris Nnenna Amuji Abimbola Mary Oluwajembola Eziuche Amadike Ugbogu |
| author_facet | Emeka Eze Joshua Iweala Doris Nnenna Amuji Abimbola Mary Oluwajembola Eziuche Amadike Ugbogu |
| author_sort | Emeka Eze Joshua Iweala |
| collection | DOAJ |
| description | Breast cancer presents a significant challenge due to its heterogeneity and propensity for developing chemoresistance, particularly in the triple-negative subtype. c-Mesenchymal epithelial transition factor (c-Met), a receptor tyrosine kinase, presents a promising target for breast cancer therapy due to its involvement in disease progression and poor prognosis. However, the heterogeneous expression of c-Met within breast cancer subtypes and individual tumors complicates targeted therapy. Also, cancer cells can develop resistance to c-Met inhibitors through various mechanisms, including bypass signaling pathways and genetic mutations. The off-target effects of c-Met inhibitors further limit their clinical utility, necessitating the development of more selective agents. To overcome these challenges, personalized treatment approaches and combination therapies are being explored to improve treatment efficacy while minimizing adverse effects. Novel c-Met inhibitors with improved selectivity and reduced off-target toxicity show promise in preclinical studies. Additionally, targeted delivery systems aim to enhance drug localization and reduce systemic toxicity. Future directions involve refining inhibitor design and integrating c-Met inhibition into personalized treatment regimens guided by molecular profiling. This review explores the mechanisms by which c-Met contributes to chemoresistance in breast cancer and current challenges in targeting c-Met for breast cancer therapy. It discusses strategies to optimize treatment outcomes, ultimately improving patient prognosis and reducing mortality rates associated with this devastating disease. |
| format | Article |
| id | doaj-art-ca2e38cd280742e2b90f470aa9fb3cad |
| institution | OA Journals |
| issn | 2590-2571 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Current Research in Pharmacology and Drug Discovery |
| spelling | doaj-art-ca2e38cd280742e2b90f470aa9fb3cad2025-08-20T02:37:45ZengElsevierCurrent Research in Pharmacology and Drug Discovery2590-25712024-01-01710020410.1016/j.crphar.2024.100204Targeting c-Met in breast cancer: From mechanisms of chemoresistance to novel therapeutic strategiesEmeka Eze Joshua Iweala0Doris Nnenna Amuji1Abimbola Mary Oluwajembola2Eziuche Amadike Ugbogu3Department of Biochemistry, College of Science and Technology, Covenant University, Ota, Nigeria; Covenant Applied Informatics and Communication Africa Centre of Excellence (CApIC-ACE), Covenant University, Ota, NigeriaDepartment of Biochemistry, College of Science and Technology, Covenant University, Ota, Nigeria; Covenant Applied Informatics and Communication Africa Centre of Excellence (CApIC-ACE), Covenant University, Ota, Nigeria; Corresponding author. Department of Biochemistry, College of Science and Technology, Covenant University, KM. 10 Idiroko Road, Canaan Land, 112104, Ota, Ogun State, Nigeria.Department of Biochemistry, College of Science and Technology, Covenant University, Ota, Nigeria; Covenant Applied Informatics and Communication Africa Centre of Excellence (CApIC-ACE), Covenant University, Ota, NigeriaDepartment of Biochemistry, Abia State University, PMB 2000, Uturu, Abia State, NigeriaBreast cancer presents a significant challenge due to its heterogeneity and propensity for developing chemoresistance, particularly in the triple-negative subtype. c-Mesenchymal epithelial transition factor (c-Met), a receptor tyrosine kinase, presents a promising target for breast cancer therapy due to its involvement in disease progression and poor prognosis. However, the heterogeneous expression of c-Met within breast cancer subtypes and individual tumors complicates targeted therapy. Also, cancer cells can develop resistance to c-Met inhibitors through various mechanisms, including bypass signaling pathways and genetic mutations. The off-target effects of c-Met inhibitors further limit their clinical utility, necessitating the development of more selective agents. To overcome these challenges, personalized treatment approaches and combination therapies are being explored to improve treatment efficacy while minimizing adverse effects. Novel c-Met inhibitors with improved selectivity and reduced off-target toxicity show promise in preclinical studies. Additionally, targeted delivery systems aim to enhance drug localization and reduce systemic toxicity. Future directions involve refining inhibitor design and integrating c-Met inhibition into personalized treatment regimens guided by molecular profiling. This review explores the mechanisms by which c-Met contributes to chemoresistance in breast cancer and current challenges in targeting c-Met for breast cancer therapy. It discusses strategies to optimize treatment outcomes, ultimately improving patient prognosis and reducing mortality rates associated with this devastating disease.http://www.sciencedirect.com/science/article/pii/S2590257124000312Breast cancerChemoresistancec-Met inhibitorsTargeted therapyPreclinical studies |
| spellingShingle | Emeka Eze Joshua Iweala Doris Nnenna Amuji Abimbola Mary Oluwajembola Eziuche Amadike Ugbogu Targeting c-Met in breast cancer: From mechanisms of chemoresistance to novel therapeutic strategies Current Research in Pharmacology and Drug Discovery Breast cancer Chemoresistance c-Met inhibitors Targeted therapy Preclinical studies |
| title | Targeting c-Met in breast cancer: From mechanisms of chemoresistance to novel therapeutic strategies |
| title_full | Targeting c-Met in breast cancer: From mechanisms of chemoresistance to novel therapeutic strategies |
| title_fullStr | Targeting c-Met in breast cancer: From mechanisms of chemoresistance to novel therapeutic strategies |
| title_full_unstemmed | Targeting c-Met in breast cancer: From mechanisms of chemoresistance to novel therapeutic strategies |
| title_short | Targeting c-Met in breast cancer: From mechanisms of chemoresistance to novel therapeutic strategies |
| title_sort | targeting c met in breast cancer from mechanisms of chemoresistance to novel therapeutic strategies |
| topic | Breast cancer Chemoresistance c-Met inhibitors Targeted therapy Preclinical studies |
| url | http://www.sciencedirect.com/science/article/pii/S2590257124000312 |
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