Destabilizing the genome as a therapeutic strategy to enhance response to immune checkpoint blockade: a systematic review of clinical trials evidence from solid and hematological tumors
Background: Genomic instability is increased alterations in the genome during cell division and is common among most cancer cells. Genome instability enhances the risk of initial carcinogenic transformation, generating new clones of tumor cells, and increases tumor heterogeneity. Although genome ins...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-01-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1280591/full |
| _version_ | 1797361386475487232 |
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| author | Faizah Alotaibi Faizah Alotaibi Kanaan Alshammari Kanaan Alshammari Kanaan Alshammari Badi A. Alotaibi Badi A. Alotaibi Hashem Alsaab |
| author_facet | Faizah Alotaibi Faizah Alotaibi Kanaan Alshammari Kanaan Alshammari Kanaan Alshammari Badi A. Alotaibi Badi A. Alotaibi Hashem Alsaab |
| author_sort | Faizah Alotaibi |
| collection | DOAJ |
| description | Background: Genomic instability is increased alterations in the genome during cell division and is common among most cancer cells. Genome instability enhances the risk of initial carcinogenic transformation, generating new clones of tumor cells, and increases tumor heterogeneity. Although genome instability contributes to malignancy, it is also an “Achilles’ heel” that constitutes a therapeutically-exploitable weakness—when sufficiently advanced, it can intrinsically reduce tumor cell survival by creating DNA damage and mutation events that overwhelm the capacity of cancer cells to repair those lesions. Furthermore, it can contribute to extrinsic survival-reducing events by generating mutations that encode new immunogenic antigens capable of being recognized by the immune system, particularly when anti-tumor immunity is boosted by immunotherapy drugs. Here, we describe how genome-destabilization can induce immune activation in cancer patients and systematically review the induction of genome instability exploited clinically, in combination with immune checkpoint blockade.Methods: We performed a systematic review of clinical trials that exploited the combination approach to successfully treat cancers patients. We systematically searched PubMed, Cochrane Central Register of Controlled Trials, Clinicaltrials.gov, and publication from the reference list of related articles. The most relevant inclusion criteria were peer-reviewed clinical trials published in English.Results: We identified 1,490 studies, among those 164 were clinical trials. A total of 37 clinical trials satisfied the inclusion criteria and were included in the study. The main outcome measurements were overall survival and progression-free survival. The majority of the clinical trials (30 out of 37) showed a significant improvement in patient outcome.Conclusion: The majority of the included clinical trials reported the efficacy of the concept of targeting DNA repair pathway, in combination with immune checkpoint inhibitors, to create a “ring of synergy” to treat cancer with rational combinations. |
| first_indexed | 2024-03-08T15:52:58Z |
| format | Article |
| id | doaj.art-b5a31a0271aa44ec8fe7637a9f4895ed |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-03-08T15:52:58Z |
| publishDate | 2024-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-b5a31a0271aa44ec8fe7637a9f4895ed2024-01-09T04:12:59ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122024-01-011410.3389/fphar.2023.12805911280591Destabilizing the genome as a therapeutic strategy to enhance response to immune checkpoint blockade: a systematic review of clinical trials evidence from solid and hematological tumorsFaizah Alotaibi0Faizah Alotaibi1Kanaan Alshammari2Kanaan Alshammari3Kanaan Alshammari4Badi A. Alotaibi5Badi A. Alotaibi6Hashem Alsaab7College of Science and Health Professions, King Saud Bin Abdulaziz University for Health Sciences, Alahsa, Saudi ArabiaKing Abdullah International Medical Research Center, Ministry of National Guard-Health Affairs, Riyadh, Saudi ArabiaKing Abdullah International Medical Research Center, Ministry of National Guard-Health Affairs, Riyadh, Saudi ArabiaOncology Department, King Abdulaziz Medical City, Ministry of National Guard-Health Affairs, Riyadh, Saudi ArabiaCollege of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi ArabiaKing Abdullah International Medical Research Center, Ministry of National Guard-Health Affairs, Riyadh, Saudi ArabiaDepartment of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi ArabiaDepartment of Pharmaceutics and Pharmaceutical Technology, Taif University, Taif, Saudi ArabiaBackground: Genomic instability is increased alterations in the genome during cell division and is common among most cancer cells. Genome instability enhances the risk of initial carcinogenic transformation, generating new clones of tumor cells, and increases tumor heterogeneity. Although genome instability contributes to malignancy, it is also an “Achilles’ heel” that constitutes a therapeutically-exploitable weakness—when sufficiently advanced, it can intrinsically reduce tumor cell survival by creating DNA damage and mutation events that overwhelm the capacity of cancer cells to repair those lesions. Furthermore, it can contribute to extrinsic survival-reducing events by generating mutations that encode new immunogenic antigens capable of being recognized by the immune system, particularly when anti-tumor immunity is boosted by immunotherapy drugs. Here, we describe how genome-destabilization can induce immune activation in cancer patients and systematically review the induction of genome instability exploited clinically, in combination with immune checkpoint blockade.Methods: We performed a systematic review of clinical trials that exploited the combination approach to successfully treat cancers patients. We systematically searched PubMed, Cochrane Central Register of Controlled Trials, Clinicaltrials.gov, and publication from the reference list of related articles. The most relevant inclusion criteria were peer-reviewed clinical trials published in English.Results: We identified 1,490 studies, among those 164 were clinical trials. A total of 37 clinical trials satisfied the inclusion criteria and were included in the study. The main outcome measurements were overall survival and progression-free survival. The majority of the clinical trials (30 out of 37) showed a significant improvement in patient outcome.Conclusion: The majority of the included clinical trials reported the efficacy of the concept of targeting DNA repair pathway, in combination with immune checkpoint inhibitors, to create a “ring of synergy” to treat cancer with rational combinations.https://www.frontiersin.org/articles/10.3389/fphar.2023.1280591/fullICIchemotherapiesclinical trailcancerradiotherapydestabilizing the genome |
| spellingShingle | Faizah Alotaibi Faizah Alotaibi Kanaan Alshammari Kanaan Alshammari Kanaan Alshammari Badi A. Alotaibi Badi A. Alotaibi Hashem Alsaab Destabilizing the genome as a therapeutic strategy to enhance response to immune checkpoint blockade: a systematic review of clinical trials evidence from solid and hematological tumors Frontiers in Pharmacology ICI chemotherapies clinical trail cancer radiotherapy destabilizing the genome |
| title | Destabilizing the genome as a therapeutic strategy to enhance response to immune checkpoint blockade: a systematic review of clinical trials evidence from solid and hematological tumors |
| title_full | Destabilizing the genome as a therapeutic strategy to enhance response to immune checkpoint blockade: a systematic review of clinical trials evidence from solid and hematological tumors |
| title_fullStr | Destabilizing the genome as a therapeutic strategy to enhance response to immune checkpoint blockade: a systematic review of clinical trials evidence from solid and hematological tumors |
| title_full_unstemmed | Destabilizing the genome as a therapeutic strategy to enhance response to immune checkpoint blockade: a systematic review of clinical trials evidence from solid and hematological tumors |
| title_short | Destabilizing the genome as a therapeutic strategy to enhance response to immune checkpoint blockade: a systematic review of clinical trials evidence from solid and hematological tumors |
| title_sort | destabilizing the genome as a therapeutic strategy to enhance response to immune checkpoint blockade a systematic review of clinical trials evidence from solid and hematological tumors |
| topic | ICI chemotherapies clinical trail cancer radiotherapy destabilizing the genome |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2023.1280591/full |
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