Targeting RTKs/nRTKs as promising therapeutic strategies for the treatment of triple-negative breast cancer: evidence from clinical trials
Abstract The extensive heterogeneity and the limited availability of effective targeted therapies contribute to the challenging prognosis and restricted survival observed in triple-negative breast cancer (TNBC). Recent research indicates the aberrant expression of diverse tyrosine kinases (TKs) with...
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BMC
2024-12-01
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| Series: | Military Medical Research |
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| Online Access: | https://doi.org/10.1186/s40779-024-00582-z |
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| author | Kasshish Mehta Mangala Hegde Sosmitha Girisa Ravichandran Vishwa Mohammed S. Alqahtani Mohamed Abbas Mehdi Shakibaei Gautam Sethi Ajaikumar B. Kunnumakkara |
| author_facet | Kasshish Mehta Mangala Hegde Sosmitha Girisa Ravichandran Vishwa Mohammed S. Alqahtani Mohamed Abbas Mehdi Shakibaei Gautam Sethi Ajaikumar B. Kunnumakkara |
| author_sort | Kasshish Mehta |
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| description | Abstract The extensive heterogeneity and the limited availability of effective targeted therapies contribute to the challenging prognosis and restricted survival observed in triple-negative breast cancer (TNBC). Recent research indicates the aberrant expression of diverse tyrosine kinases (TKs) within this cancer, contributing significantly to tumor cell proliferation, survival, invasion, and migration. The contemporary paradigm shift towards precision medicine has highlighted TKs and their receptors as promising targets for pharmacotherapy against a range of malignancies, given their pivotal roles in tumor initiation, progression, and advancement. Intensive investigations have focused on various monoclonal antibodies (mAbs) and small molecule inhibitors that specifically target proteins such as epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor (VEGFR), cellular mesenchymal-epithelial transition factor (c-MET), human epidermal growth factor receptor 2 (HER2), among others, for combating TNBC. These agents have been studied both in monotherapy and in combination with other chemotherapeutic agents. Despite these advances, a substantial terrain of unexplored potential lies within the realm of TK targeted therapeutics, which hold promise in reshaping the therapeutic landscape. This review summarizes the various TK targeted therapeutics that have undergone scrutiny as potential therapeutic interventions for TNBC, dissecting the outcomes and revelations stemming from diverse clinical investigations. A key conclusion from the umbrella clinical trials evidences the necessity for in-depth molecular characterization of TNBCs for the maximum efficiency of TK targeted therapeutics, either as standalone treatments or a combination. Moreover, our observation highlights that the outcomes of TK targeted therapeutics in TNBC are substantially influenced by the diversity of the patient cohort, emphasizing the prioritization of individual patient genetic/molecular profiles for precise TNBC patient stratification for clinical studies. |
| format | Article |
| id | doaj-art-115a9fb9250e40cba2910b5b0fb8a51c |
| institution | Kabale University |
| issn | 2054-9369 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Military Medical Research |
| spelling | doaj-art-115a9fb9250e40cba2910b5b0fb8a51c2024-12-15T12:07:36ZengBMCMilitary Medical Research2054-93692024-12-0111112510.1186/s40779-024-00582-zTargeting RTKs/nRTKs as promising therapeutic strategies for the treatment of triple-negative breast cancer: evidence from clinical trialsKasshish Mehta0Mangala Hegde1Sosmitha Girisa2Ravichandran Vishwa3Mohammed S. Alqahtani4Mohamed Abbas5Mehdi Shakibaei6Gautam Sethi7Ajaikumar B. Kunnumakkara8Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati (IITG)Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati (IITG)Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati (IITG)Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati (IITG)Radiological Sciences Department, College of Applied Medical Sciences, King Khalid UniversityElectrical Engineering Department, College of Engineering, King Khalid UniversityDepartment of Human-Anatomy, Musculoskeletal Research Group and Tumor Biology, Chair of Vegetative Anatomy, Institute of Anatomy, Ludwig-Maximilian-UniversityDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of SingaporeCancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati (IITG)Abstract The extensive heterogeneity and the limited availability of effective targeted therapies contribute to the challenging prognosis and restricted survival observed in triple-negative breast cancer (TNBC). Recent research indicates the aberrant expression of diverse tyrosine kinases (TKs) within this cancer, contributing significantly to tumor cell proliferation, survival, invasion, and migration. The contemporary paradigm shift towards precision medicine has highlighted TKs and their receptors as promising targets for pharmacotherapy against a range of malignancies, given their pivotal roles in tumor initiation, progression, and advancement. Intensive investigations have focused on various monoclonal antibodies (mAbs) and small molecule inhibitors that specifically target proteins such as epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor (VEGFR), cellular mesenchymal-epithelial transition factor (c-MET), human epidermal growth factor receptor 2 (HER2), among others, for combating TNBC. These agents have been studied both in monotherapy and in combination with other chemotherapeutic agents. Despite these advances, a substantial terrain of unexplored potential lies within the realm of TK targeted therapeutics, which hold promise in reshaping the therapeutic landscape. This review summarizes the various TK targeted therapeutics that have undergone scrutiny as potential therapeutic interventions for TNBC, dissecting the outcomes and revelations stemming from diverse clinical investigations. A key conclusion from the umbrella clinical trials evidences the necessity for in-depth molecular characterization of TNBCs for the maximum efficiency of TK targeted therapeutics, either as standalone treatments or a combination. Moreover, our observation highlights that the outcomes of TK targeted therapeutics in TNBC are substantially influenced by the diversity of the patient cohort, emphasizing the prioritization of individual patient genetic/molecular profiles for precise TNBC patient stratification for clinical studies.https://doi.org/10.1186/s40779-024-00582-zTriple-negative breast cancer (TNBC)Tyrosine kinaseClinical trialPersonalised medicineGenetic diversityPatient stratification |
| spellingShingle | Kasshish Mehta Mangala Hegde Sosmitha Girisa Ravichandran Vishwa Mohammed S. Alqahtani Mohamed Abbas Mehdi Shakibaei Gautam Sethi Ajaikumar B. Kunnumakkara Targeting RTKs/nRTKs as promising therapeutic strategies for the treatment of triple-negative breast cancer: evidence from clinical trials Military Medical Research Triple-negative breast cancer (TNBC) Tyrosine kinase Clinical trial Personalised medicine Genetic diversity Patient stratification |
| title | Targeting RTKs/nRTKs as promising therapeutic strategies for the treatment of triple-negative breast cancer: evidence from clinical trials |
| title_full | Targeting RTKs/nRTKs as promising therapeutic strategies for the treatment of triple-negative breast cancer: evidence from clinical trials |
| title_fullStr | Targeting RTKs/nRTKs as promising therapeutic strategies for the treatment of triple-negative breast cancer: evidence from clinical trials |
| title_full_unstemmed | Targeting RTKs/nRTKs as promising therapeutic strategies for the treatment of triple-negative breast cancer: evidence from clinical trials |
| title_short | Targeting RTKs/nRTKs as promising therapeutic strategies for the treatment of triple-negative breast cancer: evidence from clinical trials |
| title_sort | targeting rtks nrtks as promising therapeutic strategies for the treatment of triple negative breast cancer evidence from clinical trials |
| topic | Triple-negative breast cancer (TNBC) Tyrosine kinase Clinical trial Personalised medicine Genetic diversity Patient stratification |
| url | https://doi.org/10.1186/s40779-024-00582-z |
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