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Molecular Targeting and Rational Chemotherapy in Acute Myeloid Leukemia.

Fatemeh Pourrajab1,2, Mohamad Reza Zare-Khormizi3, Seyedhossein Hekmatimoghaddam4,5

  • 1Nutrition and Food Security Research Centre, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

Journal of Experimental Pharmacology
|June 26, 2020
PubMed
Summary

Novel combination therapies show promise for relapsed acute myeloid leukemia (AML). Combining targeted agents with standard treatments, including DNA damage inducers and epigenetic modifiers, improves outcomes for refractory AML patients.

Keywords:
acuteantineoplastic agentscombinationdrug therapygeneticsleukemiamolecular targeted therapymyeloid

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Area of Science:

  • Hematology
  • Oncology
  • Molecular Biology

Background:

  • Acute myeloid leukemia (AML) is a complex hematologic malignancy with high relapse rates.
  • Current treatment options for relapsed and/or refractory AML (RR-AML) are limited, necessitating novel therapeutic strategies.
  • Targeting single pathways is often insufficient for durable remissions in diverse AML patient populations.

Purpose of the Study:

  • To review current antineoplastic agents for AML, focusing on their genetic and molecular mechanisms.
  • To explore the role and efficacy of combination regimens in treating AML, particularly RR-AML.
  • To highlight the potential of rational drug combinations in improving cure rates for relapsed AML.

Main Methods:

  • Literature review of current antineoplastic agents and combination therapies for AML.
  • Analysis of genetic and molecular mechanisms underlying AML pathogenesis and treatment response.
  • Emphasis on the synergistic effects of combining targeted agents with conventional chemotherapy or epigenetic modifiers.

Main Results:

  • Combination therapies, including targeted agents with standard chemotherapy or hypomethylating agents, demonstrate improved outcomes in relapsed AML.
  • Synergistic effects are observed when DNA damage-inducing therapies are combined with DNA methyltransferase and histone deacetylase inhibitors.
  • Novel therapeutic agents and their metabolites exhibit unique interactions leading to enhanced clinical activity.

Conclusions:

  • Rational combination regimens are crucial for improving cure rates in relapsed and/or refractory AML.
  • Combining epigenetic modifiers with DNA-damaging agents offers a promising strategy for AML treatment.
  • Further research into molecular mechanisms and combination strategies is essential for advancing AML therapy.