Cell cycle inhibitors for the treatment of acute myeloid leukemia: a review of phase 23 clinical trials
Autor: | Naveen Pemmaraju, Tapan M. Kadia, Caitlin R. Rausch, Nadya Jammal |
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Rok vydání: | 2020 |
Předmět: |
Drug
Oncology medicine.medical_specialty media_common.quotation_subject Cyclin D Antineoplastic Agents 030226 pharmacology & pharmacy 03 medical and health sciences 0302 clinical medicine Aurora kinase Drug Development Cyclin-dependent kinase Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Animals Humans Pharmacology (medical) Molecular Targeted Therapy media_common Pharmacology biology business.industry Age Factors Myeloid leukemia Cell Cycle Checkpoints Cell cycle Clinical trial Wee1 Leukemia Myeloid Acute 030220 oncology & carcinogenesis Drug Design biology.protein business |
Zdroj: | Expert opinion on emerging drugs. 25(4) |
ISSN: | 1744-7623 |
Popis: | Introduction: Acute myeloid leukemia (AML) is a clinically heterogeneous hematologic malignancy with poor long term outcomes. Cytotoxic chemotherapy remains the backbone of therapy especially among younger patients; however the effective incorporation of targeted therapies continues to be an area of active research in an effort to improve response durations and survival. Cell cycle inhibitors (CCI) are a novel class of agents which may be of particular interest for development in patients with AML. Areas covered: We will review the concept of CCIs along with available pre-clinical and clinical data in the treatment of AML both in North America and abroad. Specific drug targets reviewed include cyclin D kinase, Aurora kinase, CHK1, and WEE1. Expert opinion: Utilization of CCIs in patients with AML is an emerging approach that has shown promise in pre-clinical models. It has been challenging to translate this concept into clinical success thus far, due to marginal single-agent activity and significant toxicity profiles, however clinical evaluation is ongoing. Addition of these agents to cytotoxic chemotherapy and other targeted therapies provides a potential combinatorial path forward for this novel class of therapies. Developing optimal combinations while balancing toxicity are among the top clinical challenges that must be overcome before we can anticipate adoption of these agents into the armamentarium of AML therapy. |
Databáze: | OpenAIRE |
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