Exploiting acquired vulnerability to develop novel treatments for cholangiocarcinoma
Abstract Cholangiocarcinoma (CCA) presents a formidable therapeutic challenge due to its extensive heterogeneity and plasticity, which inevitably lead to acquired resistance to current treatments. However, recent evidence suggests that acquired drug resistance is associated with a fitness cost resul...
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| Format: | Article |
| Language: | English |
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BMC
2024-11-01
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| Series: | Cancer Cell International |
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| Online Access: | https://doi.org/10.1186/s12935-024-03548-2 |
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| author | Sirayot Areewong Orawan Suppramote Sunisa Prasopporn Siwanon Jirawatnotai |
| author_facet | Sirayot Areewong Orawan Suppramote Sunisa Prasopporn Siwanon Jirawatnotai |
| author_sort | Sirayot Areewong |
| collection | DOAJ |
| description | Abstract Cholangiocarcinoma (CCA) presents a formidable therapeutic challenge due to its extensive heterogeneity and plasticity, which inevitably lead to acquired resistance to current treatments. However, recent evidence suggests that acquired drug resistance is associated with a fitness cost resulting from the myriad of acquired alterations under the selective pressure of the primary treatment. Consequently, CCA patients with acquired resistance are more susceptible to alternative therapies that are ineffective as monotherapies. This phenomenon, termed “acquired vulnerability,” has garnered significant interest in drug development, as the acquired alterations could potentially be exploited therapeutically. This review elucidates the modes of acquired vulnerability, methods for identifying and exploiting acquired vulnerabilities in cancer (particularly in CCA), and strategies to enhance the clinical efficacy of drug combinations by leveraging the principle of acquired vulnerability. Identifying acquired vulnerabilities may pave the way for novel drug combinations to effectively treat highly heterogeneous and adaptable malignancies such as CCA. |
| format | Article |
| id | doaj-art-7efd78df73f2495597f7d9abe7a6ae04 |
| institution | Kabale University |
| issn | 1475-2867 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj-art-7efd78df73f2495597f7d9abe7a6ae042024-11-10T12:43:17ZengBMCCancer Cell International1475-28672024-11-0124112010.1186/s12935-024-03548-2Exploiting acquired vulnerability to develop novel treatments for cholangiocarcinomaSirayot Areewong0Orawan Suppramote1Sunisa Prasopporn2Siwanon Jirawatnotai3Siriraj Center of Research Excellence (SiCORE) for Systems Pharmacology, Department of Pharmacology, Faculty of Medicine, Siriraj Hospital, Mahidol UniversityPrincess Srisavangavadhana College of Medicine, Chulabhorn Royal AcademySiriraj Center of Research Excellence (SiCORE) for Systems Pharmacology, Department of Pharmacology, Faculty of Medicine, Siriraj Hospital, Mahidol UniversitySiriraj Center of Research Excellence (SiCORE) for Systems Pharmacology, Department of Pharmacology, Faculty of Medicine, Siriraj Hospital, Mahidol UniversityAbstract Cholangiocarcinoma (CCA) presents a formidable therapeutic challenge due to its extensive heterogeneity and plasticity, which inevitably lead to acquired resistance to current treatments. However, recent evidence suggests that acquired drug resistance is associated with a fitness cost resulting from the myriad of acquired alterations under the selective pressure of the primary treatment. Consequently, CCA patients with acquired resistance are more susceptible to alternative therapies that are ineffective as monotherapies. This phenomenon, termed “acquired vulnerability,” has garnered significant interest in drug development, as the acquired alterations could potentially be exploited therapeutically. This review elucidates the modes of acquired vulnerability, methods for identifying and exploiting acquired vulnerabilities in cancer (particularly in CCA), and strategies to enhance the clinical efficacy of drug combinations by leveraging the principle of acquired vulnerability. Identifying acquired vulnerabilities may pave the way for novel drug combinations to effectively treat highly heterogeneous and adaptable malignancies such as CCA.https://doi.org/10.1186/s12935-024-03548-2Acquired vulnerabilityCancer drug resistanceCholangiocarcinomaDrug combination |
| spellingShingle | Sirayot Areewong Orawan Suppramote Sunisa Prasopporn Siwanon Jirawatnotai Exploiting acquired vulnerability to develop novel treatments for cholangiocarcinoma Cancer Cell International Acquired vulnerability Cancer drug resistance Cholangiocarcinoma Drug combination |
| title | Exploiting acquired vulnerability to develop novel treatments for cholangiocarcinoma |
| title_full | Exploiting acquired vulnerability to develop novel treatments for cholangiocarcinoma |
| title_fullStr | Exploiting acquired vulnerability to develop novel treatments for cholangiocarcinoma |
| title_full_unstemmed | Exploiting acquired vulnerability to develop novel treatments for cholangiocarcinoma |
| title_short | Exploiting acquired vulnerability to develop novel treatments for cholangiocarcinoma |
| title_sort | exploiting acquired vulnerability to develop novel treatments for cholangiocarcinoma |
| topic | Acquired vulnerability Cancer drug resistance Cholangiocarcinoma Drug combination |
| url | https://doi.org/10.1186/s12935-024-03548-2 |
| work_keys_str_mv | AT sirayotareewong exploitingacquiredvulnerabilitytodevelopnoveltreatmentsforcholangiocarcinoma AT orawansuppramote exploitingacquiredvulnerabilitytodevelopnoveltreatmentsforcholangiocarcinoma AT sunisaprasopporn exploitingacquiredvulnerabilitytodevelopnoveltreatmentsforcholangiocarcinoma AT siwanonjirawatnotai exploitingacquiredvulnerabilitytodevelopnoveltreatmentsforcholangiocarcinoma |