Potential Biomarkers for Treatment Response to the BCL-2 Inhibitor Venetoclax: State of the Art and Future Directions
Intrinsic apoptotic pathway dysregulation plays an essential role in all cancers, particularly hematologic malignancies. This role has led to the development of multiple therapeutic agents targeting this pathway. Venetoclax is a selective BCL-2 inhibitor that has been approved for the treatment of c...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-06-01
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| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/13/12/2974 |
| _version_ | 1797530197169274880 |
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| author | Haneen T. Salah Courtney D. DiNardo Marina Konopleva Joseph D. Khoury |
| author_facet | Haneen T. Salah Courtney D. DiNardo Marina Konopleva Joseph D. Khoury |
| author_sort | Haneen T. Salah |
| collection | DOAJ |
| description | Intrinsic apoptotic pathway dysregulation plays an essential role in all cancers, particularly hematologic malignancies. This role has led to the development of multiple therapeutic agents targeting this pathway. Venetoclax is a selective BCL-2 inhibitor that has been approved for the treatment of chronic lymphoid leukemia and acute myeloid leukemia. Given the reported resistance to venetoclax, understanding the mechanisms of resistance and the potential biomarkers of response is crucial to ensure optimal drug usage and improved patient outcomes. Mechanisms of resistance to venetoclax include alterations involving the BH3-binding groove, <i>BCL2</i> gene mutations affecting venetoclax binding, and activation of alternative anti-apoptotic pathways. Moreover, various potential genetic biomarkers of venetoclax resistance have been proposed, including chromosome 17p deletion, trisomy 12, and <i>TP53</i> loss or mutation. This manuscript provides an overview of biomarkers that could predict treatment response to venetoclax. |
| first_indexed | 2024-03-10T10:25:34Z |
| format | Article |
| id | doaj.art-9656a77af7ad45e5a71ed897f1060735 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T10:25:34Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-9656a77af7ad45e5a71ed897f10607352023-11-22T00:02:51ZengMDPI AGCancers2072-66942021-06-011312297410.3390/cancers13122974Potential Biomarkers for Treatment Response to the BCL-2 Inhibitor Venetoclax: State of the Art and Future DirectionsHaneen T. Salah0Courtney D. DiNardo1Marina Konopleva2Joseph D. Khoury3College of Medicine, Alfaisal University, Riyadh 11533, Saudi ArabiaDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USAIntrinsic apoptotic pathway dysregulation plays an essential role in all cancers, particularly hematologic malignancies. This role has led to the development of multiple therapeutic agents targeting this pathway. Venetoclax is a selective BCL-2 inhibitor that has been approved for the treatment of chronic lymphoid leukemia and acute myeloid leukemia. Given the reported resistance to venetoclax, understanding the mechanisms of resistance and the potential biomarkers of response is crucial to ensure optimal drug usage and improved patient outcomes. Mechanisms of resistance to venetoclax include alterations involving the BH3-binding groove, <i>BCL2</i> gene mutations affecting venetoclax binding, and activation of alternative anti-apoptotic pathways. Moreover, various potential genetic biomarkers of venetoclax resistance have been proposed, including chromosome 17p deletion, trisomy 12, and <i>TP53</i> loss or mutation. This manuscript provides an overview of biomarkers that could predict treatment response to venetoclax.https://www.mdpi.com/2072-6694/13/12/2974venetoclaxBCL-2biomarkerschemoresistancetreatment response |
| spellingShingle | Haneen T. Salah Courtney D. DiNardo Marina Konopleva Joseph D. Khoury Potential Biomarkers for Treatment Response to the BCL-2 Inhibitor Venetoclax: State of the Art and Future Directions Cancers venetoclax BCL-2 biomarkers chemoresistance treatment response |
| title | Potential Biomarkers for Treatment Response to the BCL-2 Inhibitor Venetoclax: State of the Art and Future Directions |
| title_full | Potential Biomarkers for Treatment Response to the BCL-2 Inhibitor Venetoclax: State of the Art and Future Directions |
| title_fullStr | Potential Biomarkers for Treatment Response to the BCL-2 Inhibitor Venetoclax: State of the Art and Future Directions |
| title_full_unstemmed | Potential Biomarkers for Treatment Response to the BCL-2 Inhibitor Venetoclax: State of the Art and Future Directions |
| title_short | Potential Biomarkers for Treatment Response to the BCL-2 Inhibitor Venetoclax: State of the Art and Future Directions |
| title_sort | potential biomarkers for treatment response to the bcl 2 inhibitor venetoclax state of the art and future directions |
| topic | venetoclax BCL-2 biomarkers chemoresistance treatment response |
| url | https://www.mdpi.com/2072-6694/13/12/2974 |
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