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- Title
Inhibitors of Chemoresistance Pathways in Combination with Ara-C to Overcome Multidrug Resistance in AML. A Mini Review.
- Authors
Fajardo-Orduña, Guadalupe Rosario; Ledesma-Martínez, Edgar; Aguiñiga-Sánchez, Itzen; Mora-García, María de Lourdes; Weiss-Steider, Benny; Santiago-Osorio, Edelmiro; Supuran, Claudiu T.
- Abstract
Acute myeloid leukemia (AML), the most common type of leukemia in older adults, is a heterogeneous disease that originates from the clonal expansion of undifferentiated hematopoietic progenitor cells. These cells present a remarkable variety of genes and proteins with altered expression and function. Despite significant advances in understanding the molecular panorama of AML and the development of therapies that target mutations, survival has not improved significantly, and the therapy standard is still based on highly toxic chemotherapy, which includes cytarabine (Ara-C) and allogeneic hematopoietic cell transplantation. Approximately 60% of AML patients respond favorably to these treatments and go into complete remission; however, most eventually relapse, develop refractory disease or chemoresistance, and do not survive for more than five years. Therefore, drug resistance that initially occurs in leukemic cells (primary resistance) or that develops during or after treatment (acquired resistance) has become the main obstacle to AML treatment. In this work, the main molecules responsible for generating chemoresistance to Ara-C in AML are discussed, as well as some of the newer strategies to overcome it, such as the inclusion of molecules that can induce synergistic cytotoxicity with Ara-C (MNKI-8e, emodin, metformin and niclosamide), subtoxic concentrations of chemotherapy (PD0332991), and potently antineoplastic treatments that do not damage nonmalignant cells (heteronemin or hydroxyurea + azidothymidine).
- Subjects
CYTARABINE; METFORMIN; MULTIDRUG resistance; HEMATOPOIETIC stem cell transplantation; DRUG resistance in cancer cells; ACUTE myeloid leukemia; PROTEIN expression
- Publication
International Journal of Molecular Sciences, 2021, Vol 22, Issue 9, p4955
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms22094955