Pharmacogenetics Role of Genetic Variants in Immune-Related Factors: A Systematic Review Focusing on mCRC
Pharmacogenetics plays a key role in personalized cancer treatment. Currently, the clinically available pharmacogenetic markers for metastatic colorectal cancer (mCRC) are in genes related to drug metabolism, such as DPYD for fluoropyrimidines and UGT1A1 for irinotecan. Recently, the impact of host...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-11-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/11/2468 |
| _version_ | 1827643883036606464 |
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| author | Lucia Scarabel Alessia Bignucolo Giuseppe Toffoli Erika Cecchin Elena De Mattia |
| author_facet | Lucia Scarabel Alessia Bignucolo Giuseppe Toffoli Erika Cecchin Elena De Mattia |
| author_sort | Lucia Scarabel |
| collection | DOAJ |
| description | Pharmacogenetics plays a key role in personalized cancer treatment. Currently, the clinically available pharmacogenetic markers for metastatic colorectal cancer (mCRC) are in genes related to drug metabolism, such as DPYD for fluoropyrimidines and UGT1A1 for irinotecan. Recently, the impact of host variability in inflammatory and immune-response genes on treatment response has gained considerable attention, opening innovative perspectives for optimizing tailored mCRC therapy. A literature review was performed on the predictive role of immune-related germline genetic biomarkers on pharmacological outcomes in patients with mCRC. Particularly, that for efficacy and toxicity was reported and the potential role for clinical management of patients was discussed. Most of the available data regard therapy effectiveness, while the impact on toxicity remains limited. Several studies focused on the effects of polymorphisms in genes related to antibody-dependent cellular cytotoxicity (FCGR2A, FCGR3A) and yielded promising but inconclusive results on cetuximab efficacy. The remaining published data are sparse and mainly hypothesis-generating but suggest potentially interesting topics for future pharmacogenetic studies, including innovative gene–drug interactions in a clinical context. Besides the tumor immune escape pathway, genetic markers belonging to cytokines/interleukins (IL-8 and its receptors) and angiogenic mediators (IGF1) seem to be the best investigated and hopefully most promising to be translated into clinical practice after validation. |
| first_indexed | 2024-03-09T18:04:40Z |
| format | Article |
| id | doaj.art-6f07011db1694105a85c6b8f9a33b9c7 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T18:04:40Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-6f07011db1694105a85c6b8f9a33b9c72023-11-24T09:36:18ZengMDPI AGPharmaceutics1999-49232022-11-011411246810.3390/pharmaceutics14112468Pharmacogenetics Role of Genetic Variants in Immune-Related Factors: A Systematic Review Focusing on mCRCLucia Scarabel0Alessia Bignucolo1Giuseppe Toffoli2Erika Cecchin3Elena De Mattia4Experimental and Clinical Pharmacology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, via Franco Gallini n. 2, 33081 Aviano, ItalyExperimental and Clinical Pharmacology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, via Franco Gallini n. 2, 33081 Aviano, ItalyExperimental and Clinical Pharmacology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, via Franco Gallini n. 2, 33081 Aviano, ItalyExperimental and Clinical Pharmacology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, via Franco Gallini n. 2, 33081 Aviano, ItalyExperimental and Clinical Pharmacology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, via Franco Gallini n. 2, 33081 Aviano, ItalyPharmacogenetics plays a key role in personalized cancer treatment. Currently, the clinically available pharmacogenetic markers for metastatic colorectal cancer (mCRC) are in genes related to drug metabolism, such as DPYD for fluoropyrimidines and UGT1A1 for irinotecan. Recently, the impact of host variability in inflammatory and immune-response genes on treatment response has gained considerable attention, opening innovative perspectives for optimizing tailored mCRC therapy. A literature review was performed on the predictive role of immune-related germline genetic biomarkers on pharmacological outcomes in patients with mCRC. Particularly, that for efficacy and toxicity was reported and the potential role for clinical management of patients was discussed. Most of the available data regard therapy effectiveness, while the impact on toxicity remains limited. Several studies focused on the effects of polymorphisms in genes related to antibody-dependent cellular cytotoxicity (FCGR2A, FCGR3A) and yielded promising but inconclusive results on cetuximab efficacy. The remaining published data are sparse and mainly hypothesis-generating but suggest potentially interesting topics for future pharmacogenetic studies, including innovative gene–drug interactions in a clinical context. Besides the tumor immune escape pathway, genetic markers belonging to cytokines/interleukins (IL-8 and its receptors) and angiogenic mediators (IGF1) seem to be the best investigated and hopefully most promising to be translated into clinical practice after validation.https://www.mdpi.com/1999-4923/14/11/2468colorectal cancermCRCbiomarkersgenetic susceptibility factorsimmunotherapypharmacogenetics |
| spellingShingle | Lucia Scarabel Alessia Bignucolo Giuseppe Toffoli Erika Cecchin Elena De Mattia Pharmacogenetics Role of Genetic Variants in Immune-Related Factors: A Systematic Review Focusing on mCRC Pharmaceutics colorectal cancer mCRC biomarkers genetic susceptibility factors immunotherapy pharmacogenetics |
| title | Pharmacogenetics Role of Genetic Variants in Immune-Related Factors: A Systematic Review Focusing on mCRC |
| title_full | Pharmacogenetics Role of Genetic Variants in Immune-Related Factors: A Systematic Review Focusing on mCRC |
| title_fullStr | Pharmacogenetics Role of Genetic Variants in Immune-Related Factors: A Systematic Review Focusing on mCRC |
| title_full_unstemmed | Pharmacogenetics Role of Genetic Variants in Immune-Related Factors: A Systematic Review Focusing on mCRC |
| title_short | Pharmacogenetics Role of Genetic Variants in Immune-Related Factors: A Systematic Review Focusing on mCRC |
| title_sort | pharmacogenetics role of genetic variants in immune related factors a systematic review focusing on mcrc |
| topic | colorectal cancer mCRC biomarkers genetic susceptibility factors immunotherapy pharmacogenetics |
| url | https://www.mdpi.com/1999-4923/14/11/2468 |
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