Are We Moving the Needle for Patients with TP53-Mutated Acute Myeloid Leukemia?

Cancers

Maximilian F. Stahl¹  Jan P. Bewersdorf²  Stephanie Halene³  Amer M. Zeidan³  Rory M. Shallis³ 

[1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA;Division of Hematologic Malignancies, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA;Section of Hematology, Department of Internal Medicine, Yale University School of Medicine and Yale Cancer Center, New Haven, CT 06520, USA;

关键词: acute myeloid leukemia;    AML;    leukemia;    p53;    TP53;   

DOI  :  10.3390/cancers14102434

来源: DOAJ

【 摘 要 】

The currently available therapeutic options for patients with TP53-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 TP53 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 TP53-mutated AML.

【 授权许可】

Unknown