Are We Moving the Needle for Patients with <i>TP53</i>-Mutated Acute Myeloid Leukemia?
The currently available therapeutic options for patients with <i>TP53</i>-mutated acute myeloid leukemia (AML) are insufficient, as they translate to a median overall of only 6–9 months, and less than 10% of patients undergoing the most aggressive treatments, such as intensive induction...
| Main Authors: | , , , , |
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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/2072-6694/14/10/2434 |
| _version_ | 1797501057530593280 |
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| author | Rory M. Shallis Jan P. Bewersdorf Maximilian F. Stahl Stephanie Halene Amer M. Zeidan |
| author_facet | Rory M. Shallis Jan P. Bewersdorf Maximilian F. Stahl Stephanie Halene Amer M. Zeidan |
| author_sort | Rory M. Shallis |
| collection | DOAJ |
| description | The currently available therapeutic options for patients with <i>TP53</i>-mutated acute myeloid leukemia (AML) are insufficient, as they translate to a median overall of only 6–9 months, and less than 10% of patients undergoing the most aggressive treatments, such as intensive induction therapy and allogeneic hematopoietic stem cell transplantation, will be cured. The lack of clear differences in outcomes with different treatments precludes the designation of a standard of care. Recently, there has been growing attention on this critical area of need by way of better understanding the biology of <i>TP53</i> alterations and the disparities in outcomes among patients in this molecular subgroup, reflected in the development and testing of agents with novel mechanisms of action. Promising preclinical and efficacy data exist for therapies that are directed at the p53 protein rendered dysfunctional via mutation or that inhibit the CD47/SIRPα axis or other immune checkpoints such as TIM-3. In this review, we discuss recently attractive and emerging therapeutic agents, their preclinical rationale and the available clinical data as a monotherapy or in combination with the currently accepted backbones in frontline and relapsed/refractory settings for patients with <i>TP53</i>-mutated AML. |
| first_indexed | 2024-03-10T03:12:51Z |
| format | Article |
| id | doaj.art-a7b7ce4b2b1b476a8a4334d8ae18ae8a |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T03:12:51Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-a7b7ce4b2b1b476a8a4334d8ae18ae8a2023-11-23T10:23:06ZengMDPI AGCancers2072-66942022-05-011410243410.3390/cancers14102434Are We Moving the Needle for Patients with <i>TP53</i>-Mutated Acute Myeloid Leukemia?Rory M. Shallis0Jan P. Bewersdorf1Maximilian F. Stahl2Stephanie Halene3Amer M. Zeidan4Section of Hematology, Department of Internal Medicine, Yale University School of Medicine and Yale Cancer Center, New Haven, CT 06520, USADivision of Hematologic Malignancies, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USADepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USASection of Hematology, Department of Internal Medicine, Yale University School of Medicine and Yale Cancer Center, New Haven, CT 06520, USASection of Hematology, Department of Internal Medicine, Yale University School of Medicine and Yale Cancer Center, New Haven, CT 06520, USAThe currently available therapeutic options for patients with <i>TP53</i>-mutated acute myeloid leukemia (AML) are insufficient, as they translate to a median overall of only 6–9 months, and less than 10% of patients undergoing the most aggressive treatments, such as intensive induction therapy and allogeneic hematopoietic stem cell transplantation, will be cured. The lack of clear differences in outcomes with different treatments precludes the designation of a standard of care. Recently, there has been growing attention on this critical area of need by way of better understanding the biology of <i>TP53</i> alterations and the disparities in outcomes among patients in this molecular subgroup, reflected in the development and testing of agents with novel mechanisms of action. Promising preclinical and efficacy data exist for therapies that are directed at the p53 protein rendered dysfunctional via mutation or that inhibit the CD47/SIRPα axis or other immune checkpoints such as TIM-3. In this review, we discuss recently attractive and emerging therapeutic agents, their preclinical rationale and the available clinical data as a monotherapy or in combination with the currently accepted backbones in frontline and relapsed/refractory settings for patients with <i>TP53</i>-mutated AML.https://www.mdpi.com/2072-6694/14/10/2434acute myeloid leukemiaAMLleukemiap53<i>TP53</i> |
| spellingShingle | Rory M. Shallis Jan P. Bewersdorf Maximilian F. Stahl Stephanie Halene Amer M. Zeidan Are We Moving the Needle for Patients with <i>TP53</i>-Mutated Acute Myeloid Leukemia? Cancers acute myeloid leukemia AML leukemia p53 <i>TP53</i> |
| title | Are We Moving the Needle for Patients with <i>TP53</i>-Mutated Acute Myeloid Leukemia? |
| title_full | Are We Moving the Needle for Patients with <i>TP53</i>-Mutated Acute Myeloid Leukemia? |
| title_fullStr | Are We Moving the Needle for Patients with <i>TP53</i>-Mutated Acute Myeloid Leukemia? |
| title_full_unstemmed | Are We Moving the Needle for Patients with <i>TP53</i>-Mutated Acute Myeloid Leukemia? |
| title_short | Are We Moving the Needle for Patients with <i>TP53</i>-Mutated Acute Myeloid Leukemia? |
| title_sort | are we moving the needle for patients with i tp53 i mutated acute myeloid leukemia |
| topic | acute myeloid leukemia AML leukemia p53 <i>TP53</i> |
| url | https://www.mdpi.com/2072-6694/14/10/2434 |
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