How to Best Exploit Immunotherapeutics in Advanced Gastric Cancer: Between Biomarkers and Novel Cell-Based Approaches
Despite extensive research efforts, advanced gastric cancer still has a dismal prognosis with conventional treatment options. Immune checkpoint inhibitors have revolutionized the treatment landscape for many solid tumors. Amongst gastric cancer subtypes, tumors with microsatellite instability and Ep...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-04-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/10/7/1412 |
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| author | Michele Ghidini Angelica Petrillo Andrea Botticelli Dario Trapani Alessandro Parisi Anna La Salvia Elham Sajjadi Roberto Piciotti Nicola Fusco Shelize Khakoo |
| author_facet | Michele Ghidini Angelica Petrillo Andrea Botticelli Dario Trapani Alessandro Parisi Anna La Salvia Elham Sajjadi Roberto Piciotti Nicola Fusco Shelize Khakoo |
| author_sort | Michele Ghidini |
| collection | DOAJ |
| description | Despite extensive research efforts, advanced gastric cancer still has a dismal prognosis with conventional treatment options. Immune checkpoint inhibitors have revolutionized the treatment landscape for many solid tumors. Amongst gastric cancer subtypes, tumors with microsatellite instability and Epstein Barr Virus positive tumors provide the strongest rationale for responding to immunotherapy. Various predictive biomarkers such as mismatch repair status, programmed death ligand 1 expression, tumor mutational burden, assessment of tumor infiltrating lymphocytes and circulating biomarkers have been evaluated. However, results have been inconsistent due to different methodologies and thresholds used. Clinical implementation therefore remains a challenge. The role of immune checkpoint inhibitors in gastric cancer is emerging with data from monotherapy in the heavily pre-treated population already available and studies in earlier disease settings with different combinatorial approaches in progress. Immune checkpoint inhibitor combinations with chemotherapy (CT), anti-angiogenics, tyrosine kinase inhibitors, anti-Her2 directed therapy, poly (ADP-ribose) polymerase inhibitors or dual checkpoint inhibitor strategies are being explored. Moreover, novel strategies including vaccines and CAR T cell therapy are also being trialed. Here we provide an update on predictive biomarkers for response to immunotherapy with an overview of their strengths and limitations. We discuss clinical trials that have been reported and trials in progress whilst providing an account of future steps needed to improve outcome in this lethal disease. |
| first_indexed | 2024-03-10T12:42:09Z |
| format | Article |
| id | doaj.art-0480e9a930e64a74b6737392772c7387 |
| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-10T12:42:09Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-0480e9a930e64a74b6737392772c73872023-11-21T13:43:57ZengMDPI AGJournal of Clinical Medicine2077-03832021-04-01107141210.3390/jcm10071412How to Best Exploit Immunotherapeutics in Advanced Gastric Cancer: Between Biomarkers and Novel Cell-Based ApproachesMichele Ghidini0Angelica Petrillo1Andrea Botticelli2Dario Trapani3Alessandro Parisi4Anna La Salvia5Elham Sajjadi6Roberto Piciotti7Nicola Fusco8Shelize Khakoo9Medical Oncology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, ItalyMedical Oncology Unit, Ospedale Del Mare, 80147 Naples, ItalyDepartment of Clinical and Molecular Medicine, Sapienza University, 00189 Rome, ItalyDivision of Early Drug Development for innovative therapies, European Institute of Oncology, IRCCS, 20141 Milan, ItalyDepartment of Life, Health and Environmental Sciences, University of L’Aquila, 67100 L’Aquila, ItalyDepartment of Oncology, University Hospital 12 De Octubre, 28041 Madrid, SpainDivision of Pathology, European Institute of Oncology, IRCCS, 20141 Milan, ItalyDivision of Pathology, European Institute of Oncology, IRCCS, 20141 Milan, ItalyDivision of Pathology, European Institute of Oncology, IRCCS, 20141 Milan, ItalyDepartment of Medicine, Royal Marsden Hospital, London and Surrey, Sutton SM25PT, UKDespite extensive research efforts, advanced gastric cancer still has a dismal prognosis with conventional treatment options. Immune checkpoint inhibitors have revolutionized the treatment landscape for many solid tumors. Amongst gastric cancer subtypes, tumors with microsatellite instability and Epstein Barr Virus positive tumors provide the strongest rationale for responding to immunotherapy. Various predictive biomarkers such as mismatch repair status, programmed death ligand 1 expression, tumor mutational burden, assessment of tumor infiltrating lymphocytes and circulating biomarkers have been evaluated. However, results have been inconsistent due to different methodologies and thresholds used. Clinical implementation therefore remains a challenge. The role of immune checkpoint inhibitors in gastric cancer is emerging with data from monotherapy in the heavily pre-treated population already available and studies in earlier disease settings with different combinatorial approaches in progress. Immune checkpoint inhibitor combinations with chemotherapy (CT), anti-angiogenics, tyrosine kinase inhibitors, anti-Her2 directed therapy, poly (ADP-ribose) polymerase inhibitors or dual checkpoint inhibitor strategies are being explored. Moreover, novel strategies including vaccines and CAR T cell therapy are also being trialed. Here we provide an update on predictive biomarkers for response to immunotherapy with an overview of their strengths and limitations. We discuss clinical trials that have been reported and trials in progress whilst providing an account of future steps needed to improve outcome in this lethal disease.https://www.mdpi.com/2077-0383/10/7/1412immune checkpoint inhibitorsgastric cancerEpstein Barr Virustumor mutational burdenmicrosatellite instabilitypredictive biomarkers |
| spellingShingle | Michele Ghidini Angelica Petrillo Andrea Botticelli Dario Trapani Alessandro Parisi Anna La Salvia Elham Sajjadi Roberto Piciotti Nicola Fusco Shelize Khakoo How to Best Exploit Immunotherapeutics in Advanced Gastric Cancer: Between Biomarkers and Novel Cell-Based Approaches Journal of Clinical Medicine immune checkpoint inhibitors gastric cancer Epstein Barr Virus tumor mutational burden microsatellite instability predictive biomarkers |
| title | How to Best Exploit Immunotherapeutics in Advanced Gastric Cancer: Between Biomarkers and Novel Cell-Based Approaches |
| title_full | How to Best Exploit Immunotherapeutics in Advanced Gastric Cancer: Between Biomarkers and Novel Cell-Based Approaches |
| title_fullStr | How to Best Exploit Immunotherapeutics in Advanced Gastric Cancer: Between Biomarkers and Novel Cell-Based Approaches |
| title_full_unstemmed | How to Best Exploit Immunotherapeutics in Advanced Gastric Cancer: Between Biomarkers and Novel Cell-Based Approaches |
| title_short | How to Best Exploit Immunotherapeutics in Advanced Gastric Cancer: Between Biomarkers and Novel Cell-Based Approaches |
| title_sort | how to best exploit immunotherapeutics in advanced gastric cancer between biomarkers and novel cell based approaches |
| topic | immune checkpoint inhibitors gastric cancer Epstein Barr Virus tumor mutational burden microsatellite instability predictive biomarkers |
| url | https://www.mdpi.com/2077-0383/10/7/1412 |
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