Targeting multiple signaling pathways:the new approach to acute myeloid leukemia therapy
作者机构：Cancer Biology Graduate ProgramWayne State University School of MedicineDetroitMIUSA MD/PhD ProgramWayne State University School of MedicineDetroitMIUSA Department of OncologyWayne State University School of MedicineDetroitMIUSA Molecular Therapeutics ProgramBarbara Ann Karmanos Cancer InstituteWayne State University School of MedicineDetroitMIUSA Center for Molecular Medicine and GeneticsWayne State University School of MedicineDetroitMIUSA National Engineering Laboratory for AIDS VaccineKey Laboratory for Molecular Enzymology and EngineeringThe Ministry of EducationSchool of Life SciencesJilin UniversityChangchunChina Division of Pediatric Hematology/OncologyChildren’s Hospital of MichiganDetroitMIUSA Department of PediatricsWayne State University School of MedicineDetroitMIUSA
出 版 物：《Signal Transduction and Targeted Therapy》 (信号转导与靶向治疗（英文）)
年 卷 期：2021年第6卷第1期
页 面：41-69页
核心收录：
学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100214[医学-肿瘤学] 10[医学]
基 金：National Cancer Institute, NCI, (T32CA009531) National Cancer Institute, NCI AstraZeneca Janssen Pharmaceuticals MEI Pharma
摘 要：Acute myeloid leukemia(AML)is the most common form of acute leukemia in adults and the second most common form of acute leukemia in children.Despite this,very little improvement in survival rates has been achieved over the past few decades.This is partially due to the heterogeneity of AML and the need for more targeted therapeutics than the traditional cytotoxic chemotherapies that have been a mainstay in therapy for the past 50 years.In the past 20 years,research has been diversifying the approach to treating AML by investigating molecular pathways uniquely relevant to AML cell proliferation and survival.Here we review the development of novel therapeutics in targeting apoptosis,receptor tyrosine kinase(RTK)signaling,hedgehog(HH)pathway,mitochondrial function,DNA repair,and c-Myc signaling.There has been an impressive effort into better understanding the diversity of AML cell characteristics and here we highlight important preclinical studies that have supported therapeutic development and continue to promote new ways to target AML cells.In addition,we describe clinical investigations that have led to FDA approval of new targeted AML therapies and ongoing clinical trials of novel therapies targeting AML survival pathways.We also describe the complexity of targeting leukemia stem cells(LSCs)as an approach to addressing relapse and remission in AML and targetable pathways that are unique to LSC survival.This comprehensive review details what we currently understand about the signaling pathways that support AML cell survival and the exceptional ways in which we disrupt them.
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