Homologous Recombination Repair in Biliary Tract Cancers: A Prime Target for PARP Inhibition?
Biliary tract cancers (BTCs) are a heterogeneous group of malignancies that make up ~7% of all gastrointestinal tumors. It is notably aggressive and difficult to treat; in fact, >70% of patients with BTC are diagnosed at an advanced, unresectable stage and are not amenable to curative therapy. Fo...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-05-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/10/2561 |
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| author | Chao Yin Monika Kulasekaran Tina Roy Brennan Decker Sonja Alexander Mathew Margolis Reena C. Jha Gary M. Kupfer Aiwu R. He |
| author_facet | Chao Yin Monika Kulasekaran Tina Roy Brennan Decker Sonja Alexander Mathew Margolis Reena C. Jha Gary M. Kupfer Aiwu R. He |
| author_sort | Chao Yin |
| collection | DOAJ |
| description | Biliary tract cancers (BTCs) are a heterogeneous group of malignancies that make up ~7% of all gastrointestinal tumors. It is notably aggressive and difficult to treat; in fact, >70% of patients with BTC are diagnosed at an advanced, unresectable stage and are not amenable to curative therapy. For these patients, chemotherapy has been the mainstay treatment, providing an inadequate overall survival of less than one year. Despite the boom in targeted therapies over the past decade, only a few targeted agents have been approved in BTCs (i.e., IDH1 and FGFR inhibitors), perhaps in part due to its relatively low incidence. This review will explore current data on PARP inhibitors (PARPi) used in homologous recombination deficiency (HRD), particularly with respect to BTCs. Greater than 28% of BTC cases harbor mutations in genes involved in homologous recombination repair (HRR). We will summarize the mechanisms for PARPi and its role in synthetic lethality and describe select genes in the HRR pathway contributing to HRD. We will provide our rationale for expanding patient eligibility for PARPi use based on literature and anecdotal evidence pertaining to mutations in HRR genes, such as <i>RAD</i>51C, and the potential use of reliable surrogate markers of HRD. |
| first_indexed | 2024-03-10T03:11:56Z |
| format | Article |
| id | doaj.art-c00a963c2fd94324bc76d41b1c2e4b18 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T03:11:56Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-c00a963c2fd94324bc76d41b1c2e4b182023-11-23T10:24:55ZengMDPI AGCancers2072-66942022-05-011410256110.3390/cancers14102561Homologous Recombination Repair in Biliary Tract Cancers: A Prime Target for PARP Inhibition?Chao Yin0Monika Kulasekaran1Tina Roy2Brennan Decker3Sonja Alexander4Mathew Margolis5Reena C. Jha6Gary M. Kupfer7Aiwu R. He8Ruesch Center for the Cure of Gastrointestinal Cancers, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20007, USARuesch Center for the Cure of Gastrointestinal Cancers, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20007, USARuesch Center for the Cure of Gastrointestinal Cancers, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20007, USAFoundation Medicine, Cambridge, MA 20007, USAFoundation Medicine, Cambridge, MA 20007, USAFoundation Medicine, Cambridge, MA 20007, USADepartment of Radiology, Georgetown University Medical Center, Washington, DC 20007, USADepartments of Oncology and Pediatrics, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20007, USARuesch Center for the Cure of Gastrointestinal Cancers, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20007, USABiliary tract cancers (BTCs) are a heterogeneous group of malignancies that make up ~7% of all gastrointestinal tumors. It is notably aggressive and difficult to treat; in fact, >70% of patients with BTC are diagnosed at an advanced, unresectable stage and are not amenable to curative therapy. For these patients, chemotherapy has been the mainstay treatment, providing an inadequate overall survival of less than one year. Despite the boom in targeted therapies over the past decade, only a few targeted agents have been approved in BTCs (i.e., IDH1 and FGFR inhibitors), perhaps in part due to its relatively low incidence. This review will explore current data on PARP inhibitors (PARPi) used in homologous recombination deficiency (HRD), particularly with respect to BTCs. Greater than 28% of BTC cases harbor mutations in genes involved in homologous recombination repair (HRR). We will summarize the mechanisms for PARPi and its role in synthetic lethality and describe select genes in the HRR pathway contributing to HRD. We will provide our rationale for expanding patient eligibility for PARPi use based on literature and anecdotal evidence pertaining to mutations in HRR genes, such as <i>RAD</i>51C, and the potential use of reliable surrogate markers of HRD.https://www.mdpi.com/2072-6694/14/10/2561homologous recombination repairDNA damage repairPARP inhibitorbiliary tract cancersynthetic lethality |
| spellingShingle | Chao Yin Monika Kulasekaran Tina Roy Brennan Decker Sonja Alexander Mathew Margolis Reena C. Jha Gary M. Kupfer Aiwu R. He Homologous Recombination Repair in Biliary Tract Cancers: A Prime Target for PARP Inhibition? Cancers homologous recombination repair DNA damage repair PARP inhibitor biliary tract cancer synthetic lethality |
| title | Homologous Recombination Repair in Biliary Tract Cancers: A Prime Target for PARP Inhibition? |
| title_full | Homologous Recombination Repair in Biliary Tract Cancers: A Prime Target for PARP Inhibition? |
| title_fullStr | Homologous Recombination Repair in Biliary Tract Cancers: A Prime Target for PARP Inhibition? |
| title_full_unstemmed | Homologous Recombination Repair in Biliary Tract Cancers: A Prime Target for PARP Inhibition? |
| title_short | Homologous Recombination Repair in Biliary Tract Cancers: A Prime Target for PARP Inhibition? |
| title_sort | homologous recombination repair in biliary tract cancers a prime target for parp inhibition |
| topic | homologous recombination repair DNA damage repair PARP inhibitor biliary tract cancer synthetic lethality |
| url | https://www.mdpi.com/2072-6694/14/10/2561 |
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