Colorectal Cancer Heterogeneity and the Impact on Precision Medicine and Therapy Efficacy
Novel targeted therapies for metastatic colorectal cancer are needed to personalize treatments by guiding specific biomarkers selected on the genetic profile of patients. <i>RAS</i> and <i>BRAF</i> inhibitors have been developed for patients who become unresponsive to standar...
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MDPI AG
2022-04-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/10/5/1035 |
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| author | Gerardo Rosati Giuseppe Aprile Alfredo Colombo Stefano Cordio Marianna Giampaglia Alessandro Cappetta Concetta Maria Porretto Alfonso De Stefano Domenico Bilancia Antonio Avallone |
| author_facet | Gerardo Rosati Giuseppe Aprile Alfredo Colombo Stefano Cordio Marianna Giampaglia Alessandro Cappetta Concetta Maria Porretto Alfonso De Stefano Domenico Bilancia Antonio Avallone |
| author_sort | Gerardo Rosati |
| collection | DOAJ |
| description | Novel targeted therapies for metastatic colorectal cancer are needed to personalize treatments by guiding specific biomarkers selected on the genetic profile of patients. <i>RAS</i> and <i>BRAF</i> inhibitors have been developed for patients who become unresponsive to standard therapies. Sotorasib and adagrasib showed promising results in phase I/II basket trial and a phase III trial was planned with a combination of these <i>RAS</i> inhibitors and anti-<i>EGFR</i> monoclonal antibodies. Encorafenib and binimetinib were administered in phase II clinical trials for <i>BRAF</i> mutated patients. Pembrolizumab is now recommended in patients exhibiting microsatellite instability. Larotrectinib and entrectinib showed a fast and durable response with few and reversible adverse events in cases with <i>NTRK</i> fusions. Trastuzumab and trastuzumab deruxtecan exhibited promising and durable activity in <i>HER-2</i>-positive patients. In this review, the reasons for an extension of the molecular profile of patients were assessed and placed in the context of the advancements in the understanding of genetics. We highlight the differential effect of new targeted therapies through an ever-deeper characterization of tumor tissue. An overview of ongoing clinical trials is also provided. |
| first_indexed | 2024-03-10T03:17:09Z |
| format | Article |
| id | doaj.art-11352cc258214c51ab2b246869c379dd |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T03:17:09Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-11352cc258214c51ab2b246869c379dd2023-11-23T10:10:06ZengMDPI AGBiomedicines2227-90592022-04-01105103510.3390/biomedicines10051035Colorectal Cancer Heterogeneity and the Impact on Precision Medicine and Therapy EfficacyGerardo Rosati0Giuseppe Aprile1Alfredo Colombo2Stefano Cordio3Marianna Giampaglia4Alessandro Cappetta5Concetta Maria Porretto6Alfonso De Stefano7Domenico Bilancia8Antonio Avallone9Medical Oncology Unit, “S. Carlo” Hospital, 85100 Potenza, ItalyDepartment of Oncology, “San Bortolo” General Hospital, Azienda ULSS8 Berica, 36100 Vicenza, ItalyMedical Oncology Unit, CDC Macchiarella, 90138 Palermo, ItalyMedical Oncology Unit, “Maria Paternò Arezzo” Hospital, 97100 Ragusa, ItalyMedical Oncology Unit, “S. Carlo” Hospital, 85100 Potenza, ItalyDepartment of Oncology, “San Bortolo” General Hospital, Azienda ULSS8 Berica, 36100 Vicenza, ItalyMedical Oncology Unit, CDC Macchiarella, 90138 Palermo, ItalyExperimental Clinical Abdominal Oncology Unit, Istituto Nazionale Tumori IRCCS-Fondazione “G. Pascale”, 80121 Napoli, ItalyMedical Oncology Unit, “S. Carlo” Hospital, 85100 Potenza, ItalyExperimental Clinical Abdominal Oncology Unit, Istituto Nazionale Tumori IRCCS-Fondazione “G. Pascale”, 80121 Napoli, ItalyNovel targeted therapies for metastatic colorectal cancer are needed to personalize treatments by guiding specific biomarkers selected on the genetic profile of patients. <i>RAS</i> and <i>BRAF</i> inhibitors have been developed for patients who become unresponsive to standard therapies. Sotorasib and adagrasib showed promising results in phase I/II basket trial and a phase III trial was planned with a combination of these <i>RAS</i> inhibitors and anti-<i>EGFR</i> monoclonal antibodies. Encorafenib and binimetinib were administered in phase II clinical trials for <i>BRAF</i> mutated patients. Pembrolizumab is now recommended in patients exhibiting microsatellite instability. Larotrectinib and entrectinib showed a fast and durable response with few and reversible adverse events in cases with <i>NTRK</i> fusions. Trastuzumab and trastuzumab deruxtecan exhibited promising and durable activity in <i>HER-2</i>-positive patients. In this review, the reasons for an extension of the molecular profile of patients were assessed and placed in the context of the advancements in the understanding of genetics. We highlight the differential effect of new targeted therapies through an ever-deeper characterization of tumor tissue. An overview of ongoing clinical trials is also provided.https://www.mdpi.com/2227-9059/10/5/1035metastatic colorectal cancerprecision medicine<i>RAS</i> and <i>BRAF</i> inhibitorsimmunotherapyanti-<i>HER-2</i><i>TRK</i> inhibitors |
| spellingShingle | Gerardo Rosati Giuseppe Aprile Alfredo Colombo Stefano Cordio Marianna Giampaglia Alessandro Cappetta Concetta Maria Porretto Alfonso De Stefano Domenico Bilancia Antonio Avallone Colorectal Cancer Heterogeneity and the Impact on Precision Medicine and Therapy Efficacy Biomedicines metastatic colorectal cancer precision medicine <i>RAS</i> and <i>BRAF</i> inhibitors immunotherapy anti-<i>HER-2</i> <i>TRK</i> inhibitors |
| title | Colorectal Cancer Heterogeneity and the Impact on Precision Medicine and Therapy Efficacy |
| title_full | Colorectal Cancer Heterogeneity and the Impact on Precision Medicine and Therapy Efficacy |
| title_fullStr | Colorectal Cancer Heterogeneity and the Impact on Precision Medicine and Therapy Efficacy |
| title_full_unstemmed | Colorectal Cancer Heterogeneity and the Impact on Precision Medicine and Therapy Efficacy |
| title_short | Colorectal Cancer Heterogeneity and the Impact on Precision Medicine and Therapy Efficacy |
| title_sort | colorectal cancer heterogeneity and the impact on precision medicine and therapy efficacy |
| topic | metastatic colorectal cancer precision medicine <i>RAS</i> and <i>BRAF</i> inhibitors immunotherapy anti-<i>HER-2</i> <i>TRK</i> inhibitors |
| url | https://www.mdpi.com/2227-9059/10/5/1035 |
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