Kasshish Mehta, Mangala Hegde, Sosmitha Girisa, Ravichandran Vishwa, Mohammed S Alqahtani, Mohamed Abbas, Mehdi Shakibaei, Gautam Sethi, Ajaikumar B Kunnumakkara
{"title":"靶向RTKs/nRTKs作为治疗三阴性乳腺癌的有希望的治疗策略:来自临床试验的证据","authors":"Kasshish Mehta, Mangala Hegde, Sosmitha Girisa, Ravichandran Vishwa, Mohammed S Alqahtani, Mohamed Abbas, Mehdi Shakibaei, Gautam Sethi, Ajaikumar B Kunnumakkara","doi":"10.1186/s40779-024-00582-z","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"11 1","pages":"76"},"PeriodicalIF":16.7000,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11636053/pdf/","citationCount":"0","resultStr":"{\"title\":\"Targeting RTKs/nRTKs as promising therapeutic strategies for the treatment of triple-negative breast cancer: evidence from clinical trials.\",\"authors\":\"Kasshish Mehta, Mangala Hegde, Sosmitha Girisa, Ravichandran Vishwa, Mohammed S Alqahtani, Mohamed Abbas, Mehdi Shakibaei, Gautam Sethi, Ajaikumar B Kunnumakkara\",\"doi\":\"10.1186/s40779-024-00582-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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. 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Targeting RTKs/nRTKs as promising therapeutic strategies for the treatment of triple-negative breast cancer: evidence from clinical trials.
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.
期刊介绍:
Military Medical Research is an open-access, peer-reviewed journal that aims to share the most up-to-date evidence and innovative discoveries in a wide range of fields, including basic and clinical sciences, translational research, precision medicine, emerging interdisciplinary subjects, and advanced technologies. Our primary focus is on modern military medicine; however, we also encourage submissions from other related areas. This includes, but is not limited to, basic medical research with the potential for translation into practice, as well as clinical research that could impact medical care both in times of warfare and during peacetime military operations.