Intratumoral heterogeneity drives acquired therapy resistance in a patient with metastatic prostate cancer
Abstract Metastatic prostate cancer (PCa) is not curable due to its ability to acquire therapy resistance. Theoretically, acquired therapy resistance can be driven by changes to previously sensitive cancer cells or their environment and/or by outgrowth of a subpopulation of cancer cells with primary...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-12-01
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| Series: | npj Precision Oncology |
| Online Access: | https://doi.org/10.1038/s41698-024-00773-w |
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| author | Dena P. Rhinehart Jiaying Lai David E. Sanin Varsha Vakkala Adrianna Mendes Christopher Bailey Emmanuel S. Antonarakis Channing J. Paller Xiaojun Wu Tamara L. Lotan Rachel Karchin Laura A. Sena |
| author_facet | Dena P. Rhinehart Jiaying Lai David E. Sanin Varsha Vakkala Adrianna Mendes Christopher Bailey Emmanuel S. Antonarakis Channing J. Paller Xiaojun Wu Tamara L. Lotan Rachel Karchin Laura A. Sena |
| author_sort | Dena P. Rhinehart |
| collection | DOAJ |
| description | Abstract Metastatic prostate cancer (PCa) is not curable due to its ability to acquire therapy resistance. Theoretically, acquired therapy resistance can be driven by changes to previously sensitive cancer cells or their environment and/or by outgrowth of a subpopulation of cancer cells with primary resistance. Direct demonstration of the latter mechanism in patients with PCa is lacking. Here we present a case report as proof-of-principle that outgrowth of a subpopulation of cancer cells lacking the genomic target and present prior to therapy initiation can drive acquired resistance to targeted therapy and threaten survival in patients with PCa. |
| format | Article |
| id | doaj-art-cfa69be4bab4442d968155aec14047a4 |
| institution | OA Journals |
| issn | 2397-768X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Precision Oncology |
| spelling | doaj-art-cfa69be4bab4442d968155aec14047a42025-08-20T02:30:51ZengNature Portfolionpj Precision Oncology2397-768X2024-12-01811510.1038/s41698-024-00773-wIntratumoral heterogeneity drives acquired therapy resistance in a patient with metastatic prostate cancerDena P. Rhinehart0Jiaying Lai1David E. Sanin2Varsha Vakkala3Adrianna Mendes4Christopher Bailey5Emmanuel S. Antonarakis6Channing J. Paller7Xiaojun Wu8Tamara L. Lotan9Rachel Karchin10Laura A. Sena11The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins UniversityInstitute for Computational Medicine at Johns Hopkins UniversityThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins UniversityThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins UniversityThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins UniversityThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins UniversityUniversity of Minnesota Masonic Cancer CenterThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins UniversityThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins UniversityThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins UniversityInstitute for Computational Medicine at Johns Hopkins UniversityThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins UniversityAbstract Metastatic prostate cancer (PCa) is not curable due to its ability to acquire therapy resistance. Theoretically, acquired therapy resistance can be driven by changes to previously sensitive cancer cells or their environment and/or by outgrowth of a subpopulation of cancer cells with primary resistance. Direct demonstration of the latter mechanism in patients with PCa is lacking. Here we present a case report as proof-of-principle that outgrowth of a subpopulation of cancer cells lacking the genomic target and present prior to therapy initiation can drive acquired resistance to targeted therapy and threaten survival in patients with PCa.https://doi.org/10.1038/s41698-024-00773-w |
| spellingShingle | Dena P. Rhinehart Jiaying Lai David E. Sanin Varsha Vakkala Adrianna Mendes Christopher Bailey Emmanuel S. Antonarakis Channing J. Paller Xiaojun Wu Tamara L. Lotan Rachel Karchin Laura A. Sena Intratumoral heterogeneity drives acquired therapy resistance in a patient with metastatic prostate cancer npj Precision Oncology |
| title | Intratumoral heterogeneity drives acquired therapy resistance in a patient with metastatic prostate cancer |
| title_full | Intratumoral heterogeneity drives acquired therapy resistance in a patient with metastatic prostate cancer |
| title_fullStr | Intratumoral heterogeneity drives acquired therapy resistance in a patient with metastatic prostate cancer |
| title_full_unstemmed | Intratumoral heterogeneity drives acquired therapy resistance in a patient with metastatic prostate cancer |
| title_short | Intratumoral heterogeneity drives acquired therapy resistance in a patient with metastatic prostate cancer |
| title_sort | intratumoral heterogeneity drives acquired therapy resistance in a patient with metastatic prostate cancer |
| url | https://doi.org/10.1038/s41698-024-00773-w |
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