Successes and failures of angiogenesis blockade in gastric and gastro-esophageal junction adenocarcinoma
Gastric and gastro-esophageal junction adenocarcinoma (GEA) remains a considerable major public health problem worldwide, being the fifth most common cancer with a fatality-to-case ratio that stands still at 70%. Angiogenesis, which is a well-established cancer hallmark, exerts a fundamental role in...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.993573/full |
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| author | Massimiliano Salati Massimiliano Salati Francesco Caputo Alessandro Bocconi Sara Cerri Cinzia Baldessari Federico Piacentini Massimo Dominici Fabio Gelsomino |
| author_facet | Massimiliano Salati Massimiliano Salati Francesco Caputo Alessandro Bocconi Sara Cerri Cinzia Baldessari Federico Piacentini Massimo Dominici Fabio Gelsomino |
| author_sort | Massimiliano Salati |
| collection | DOAJ |
| description | Gastric and gastro-esophageal junction adenocarcinoma (GEA) remains a considerable major public health problem worldwide, being the fifth most common cancer with a fatality-to-case ratio that stands still at 70%. Angiogenesis, which is a well-established cancer hallmark, exerts a fundamental role in cancer initiation and progression and its targeting has been actively pursued as a promising therapeutic strategy in GEA. A wealth of clinical trials has been conducted, investigating anti-angiogenic agents including VEGF-directed monoclonal antibodies, small molecules tyrosine kinase inhibitors and VEGF-Trap agents both in the resectable and advanced setting, reporting controversial results. While phase III randomized trials testing the anti-VEGFR-2 antibody Ramucirumab and the selective VEGFR-2 tyrosine kinase inhibitor Apatinib demonstrated a significant survival benefit in later lines, the shift of angiogenesis inhibitors in the perioperative and first-line setting failed to improve patients’ outcome in GEAs. The molecular landscape of disease, together with novel combinatorial strategies and biomarker-selected approaches are under investigation as key elements to the success of angiogenesis blockade in GEA. In this article, we critically review the existing literature on the biological rationale and clinical development of antiangiogenic agents in GEA, discussing major achievements, limitations and future developments, aiming at fully realizing the potential of this therapeutic approach. |
| first_indexed | 2024-04-11T11:36:24Z |
| format | Article |
| id | doaj.art-0a98964771fb47139997ce8e05dc747b |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-11T11:36:24Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-0a98964771fb47139997ce8e05dc747b2022-12-22T04:25:56ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-09-011210.3389/fonc.2022.993573993573Successes and failures of angiogenesis blockade in gastric and gastro-esophageal junction adenocarcinomaMassimiliano Salati0Massimiliano Salati1Francesco Caputo2Alessandro Bocconi3Sara Cerri4Cinzia Baldessari5Federico Piacentini6Massimo Dominici7Fabio Gelsomino8Division of Oncology, Department of Oncology and Hematology, University Hospital of Modena, Modena, ItalyPhD Program Clinical and Experimental Medicine, University of Modena and Reggio Emilia, Modena, ItalyDivision of Oncology, Department of Oncology and Hematology, University Hospital of Modena, Modena, ItalyDivision of Oncology, Department of Oncology and Hematology, University Hospital of Modena, Modena, ItalyDivision of Oncology, Department of Oncology and Hematology, University Hospital of Modena, Modena, ItalyDivision of Oncology, Department of Oncology and Hematology, University Hospital of Modena, Modena, ItalyDivision of Oncology, Department of Oncology and Hematology, University Hospital of Modena, Modena, ItalyDivision of Oncology, Department of Oncology and Hematology, University Hospital of Modena, Modena, ItalyDivision of Oncology, Department of Oncology and Hematology, University Hospital of Modena, Modena, ItalyGastric and gastro-esophageal junction adenocarcinoma (GEA) remains a considerable major public health problem worldwide, being the fifth most common cancer with a fatality-to-case ratio that stands still at 70%. Angiogenesis, which is a well-established cancer hallmark, exerts a fundamental role in cancer initiation and progression and its targeting has been actively pursued as a promising therapeutic strategy in GEA. A wealth of clinical trials has been conducted, investigating anti-angiogenic agents including VEGF-directed monoclonal antibodies, small molecules tyrosine kinase inhibitors and VEGF-Trap agents both in the resectable and advanced setting, reporting controversial results. While phase III randomized trials testing the anti-VEGFR-2 antibody Ramucirumab and the selective VEGFR-2 tyrosine kinase inhibitor Apatinib demonstrated a significant survival benefit in later lines, the shift of angiogenesis inhibitors in the perioperative and first-line setting failed to improve patients’ outcome in GEAs. The molecular landscape of disease, together with novel combinatorial strategies and biomarker-selected approaches are under investigation as key elements to the success of angiogenesis blockade in GEA. In this article, we critically review the existing literature on the biological rationale and clinical development of antiangiogenic agents in GEA, discussing major achievements, limitations and future developments, aiming at fully realizing the potential of this therapeutic approach.https://www.frontiersin.org/articles/10.3389/fonc.2022.993573/fullgastric cancerangiogenesistargeted therapyprecision medicineclinical trialsgastro-esophageal adenocarcinoma |
| spellingShingle | Massimiliano Salati Massimiliano Salati Francesco Caputo Alessandro Bocconi Sara Cerri Cinzia Baldessari Federico Piacentini Massimo Dominici Fabio Gelsomino Successes and failures of angiogenesis blockade in gastric and gastro-esophageal junction adenocarcinoma Frontiers in Oncology gastric cancer angiogenesis targeted therapy precision medicine clinical trials gastro-esophageal adenocarcinoma |
| title | Successes and failures of angiogenesis blockade in gastric and gastro-esophageal junction adenocarcinoma |
| title_full | Successes and failures of angiogenesis blockade in gastric and gastro-esophageal junction adenocarcinoma |
| title_fullStr | Successes and failures of angiogenesis blockade in gastric and gastro-esophageal junction adenocarcinoma |
| title_full_unstemmed | Successes and failures of angiogenesis blockade in gastric and gastro-esophageal junction adenocarcinoma |
| title_short | Successes and failures of angiogenesis blockade in gastric and gastro-esophageal junction adenocarcinoma |
| title_sort | successes and failures of angiogenesis blockade in gastric and gastro esophageal junction adenocarcinoma |
| topic | gastric cancer angiogenesis targeted therapy precision medicine clinical trials gastro-esophageal adenocarcinoma |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.993573/full |
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