The Potential for Targeting AVIL and Other Actin-Binding Proteins in Rhabdomyosarcoma
Rhabdomyosarcoma (RMS) is the most common pediatric soft-tissue cancer with a survival rate below 27% for high-risk children despite aggressive multi-modal therapeutic interventions. After decades of research, no targeted therapies are currently available. Therapeutically targeting actin-binding pro...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/18/14196 |
| _version_ | 1797579674819231744 |
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| author | Robert Cornelison Laine Marrah Adelaide Fierti Claire Piczak Martyna Glowczyk Anam Tajammal Sarah Lynch Hui Li |
| author_facet | Robert Cornelison Laine Marrah Adelaide Fierti Claire Piczak Martyna Glowczyk Anam Tajammal Sarah Lynch Hui Li |
| author_sort | Robert Cornelison |
| collection | DOAJ |
| description | Rhabdomyosarcoma (RMS) is the most common pediatric soft-tissue cancer with a survival rate below 27% for high-risk children despite aggressive multi-modal therapeutic interventions. After decades of research, no targeted therapies are currently available. Therapeutically targeting actin-binding proteins, although promising, has historically been challenging. Recent advances have made this possibility more salient, including our lab’s identification of advillin (AVIL), a novel oncogenic actin-binding protein that plays a role in many cytoskeletal functions. AVIL is overexpressed in many RMS cell lines, patient-derived xenograft models, and a cohort of 30 clinical samples of both the alveolar (ARMS) and embryonal (ERMS) subtypes. Overexpression of AVIL in mesenchymal stem cells induces neoplastic transformation both in vitro and in vivo, and reversing overexpression through genetic modulation reverses the transformation. This suggests a critical role of AVIL in RMS tumorigenesis and maintenance. As an actin-binding protein, AVIL would not traditionally be considered a druggable target. This perspective will address the feasibility of targeting differentially expressed actin-binding proteins such as AVIL therapeutically, and how critical cell infrastructure can be damaged in a cancer-specific manner. |
| first_indexed | 2024-03-10T22:39:31Z |
| format | Article |
| id | doaj.art-a8ca2db8766e445688d7d3b0d3ccfb06 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T22:39:31Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a8ca2db8766e445688d7d3b0d3ccfb062023-11-19T11:09:14ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-09-0124181419610.3390/ijms241814196The Potential for Targeting AVIL and Other Actin-Binding Proteins in RhabdomyosarcomaRobert Cornelison0Laine Marrah1Adelaide Fierti2Claire Piczak3Martyna Glowczyk4Anam Tajammal5Sarah Lynch6Hui Li7Department of Pathology, School of Medicine, University of Virginia, Charlottesville, VA 22908, USADepartment of Pathology, School of Medicine, University of Virginia, Charlottesville, VA 22908, USADepartment of Pathology, School of Medicine, University of Virginia, Charlottesville, VA 22908, USADepartment of Pathology, School of Medicine, University of Virginia, Charlottesville, VA 22908, USADepartment of Pathology, School of Medicine, University of Virginia, Charlottesville, VA 22908, USADepartment of Pathology, School of Medicine, University of Virginia, Charlottesville, VA 22908, USADepartment of Pathology, School of Medicine, University of Virginia, Charlottesville, VA 22908, USADepartment of Pathology, School of Medicine, University of Virginia, Charlottesville, VA 22908, USARhabdomyosarcoma (RMS) is the most common pediatric soft-tissue cancer with a survival rate below 27% for high-risk children despite aggressive multi-modal therapeutic interventions. After decades of research, no targeted therapies are currently available. Therapeutically targeting actin-binding proteins, although promising, has historically been challenging. Recent advances have made this possibility more salient, including our lab’s identification of advillin (AVIL), a novel oncogenic actin-binding protein that plays a role in many cytoskeletal functions. AVIL is overexpressed in many RMS cell lines, patient-derived xenograft models, and a cohort of 30 clinical samples of both the alveolar (ARMS) and embryonal (ERMS) subtypes. Overexpression of AVIL in mesenchymal stem cells induces neoplastic transformation both in vitro and in vivo, and reversing overexpression through genetic modulation reverses the transformation. This suggests a critical role of AVIL in RMS tumorigenesis and maintenance. As an actin-binding protein, AVIL would not traditionally be considered a druggable target. This perspective will address the feasibility of targeting differentially expressed actin-binding proteins such as AVIL therapeutically, and how critical cell infrastructure can be damaged in a cancer-specific manner.https://www.mdpi.com/1422-0067/24/18/14196rhabdomyosarcomapediatric canceractin-binding proteinadvillinAVIL |
| spellingShingle | Robert Cornelison Laine Marrah Adelaide Fierti Claire Piczak Martyna Glowczyk Anam Tajammal Sarah Lynch Hui Li The Potential for Targeting AVIL and Other Actin-Binding Proteins in Rhabdomyosarcoma International Journal of Molecular Sciences rhabdomyosarcoma pediatric cancer actin-binding protein advillin AVIL |
| title | The Potential for Targeting AVIL and Other Actin-Binding Proteins in Rhabdomyosarcoma |
| title_full | The Potential for Targeting AVIL and Other Actin-Binding Proteins in Rhabdomyosarcoma |
| title_fullStr | The Potential for Targeting AVIL and Other Actin-Binding Proteins in Rhabdomyosarcoma |
| title_full_unstemmed | The Potential for Targeting AVIL and Other Actin-Binding Proteins in Rhabdomyosarcoma |
| title_short | The Potential for Targeting AVIL and Other Actin-Binding Proteins in Rhabdomyosarcoma |
| title_sort | potential for targeting avil and other actin binding proteins in rhabdomyosarcoma |
| topic | rhabdomyosarcoma pediatric cancer actin-binding protein advillin AVIL |
| url | https://www.mdpi.com/1422-0067/24/18/14196 |
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