Inhibitors of Chemoresistance Pathways in Combination with Ara-C to Overcome Multidrug Resistance in AML. A Mini Review
Por:
Fajardo-Orduna, Guadalupe Rosario, Ledesma-Martinez, Edgar, Aguiniga-Sanchez, Itzen, Mora-Garcia, Maria de Lourdes, Weiss-Steider, Benny, Santiago-Osorio, Edelmiro
Publicada:
1 may 2021
Resumen:
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).
Filiaciones:
Fajardo-Orduna, Guadalupe Rosario:
Univ Nacl Autonoma Mexico, Res Unit Cell Differentiat & Canc, Hematopoiesis & Leukemia Lab, FES Zaragoza, Mexico City 09230, DF, Mexico
Ledesma-Martinez, Edgar:
Univ Nacl Autonoma Mexico, Res Unit Cell Differentiat & Canc, Hematopoiesis & Leukemia Lab, FES Zaragoza, Mexico City 09230, DF, Mexico
Aguiniga-Sanchez, Itzen:
Univ Nacl Autonoma Mexico, Res Unit Cell Differentiat & Canc, Hematopoiesis & Leukemia Lab, FES Zaragoza, Mexico City 09230, DF, Mexico
Univ Nacl Autonoma Mexico, Sch Med, Fac High Studies Zaragoza, Dept Biomed Sci, Mexico City 09230, DF, Mexico
Mora-Garcia, Maria de Lourdes:
Univ Nacl Autonoma Mexico, Res Unit Cell Differentiat & Canc, Immunobiol Lab, FES Zaragoza, Mexico City 09230, DF, Mexico
Weiss-Steider, Benny:
Univ Nacl Autonoma Mexico, Res Unit Cell Differentiat & Canc, Hematopoiesis & Leukemia Lab, FES Zaragoza, Mexico City 09230, DF, Mexico
Santiago-Osorio, Edelmiro:
Univ Nacl Autonoma Mexico, Res Unit Cell Differentiat & Canc, Hematopoiesis & Leukemia Lab, FES Zaragoza, Mexico City 09230, DF, Mexico
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