Evidence map›Paper›PMID 30953707›Full record

ReviewCancer letters2019

Partnering with PARP inhibitors in acute myeloid leukemia with FLT3-ITD.

Anna J Dellomo, Maria R Baer, Feyruz V Rassool

Open access · greenAbstract readReview
In one paragraph

Review in Cancer letters, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.4field-weighted citation impact, top 17% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 22 citations in OpenAlex.

  1. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 2 institutions in 1 country.

Anna J DellomoDepartment of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA; University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD, 21201, USA.
Maria R BaerDepartment of Medicine, University of Maryland School of Medicine, Baltimore, MD, 21201, USA; University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD, 21201, USA; Veterans Affairs Medical Center, Baltimore, MD, 20201, USA.
Feyruz V RassoolDepartment of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA; University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD, 21201, USA. Electronic address: frassool@som.umaryland.edu.
University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer CenterVeterans Health Administration · US

Funding

UNIVERSITY OF MARYLAND GREENEBAUM CANCER CENTERSUPPORT GRANTP30CA134274 · NCI · UNIVERSITY OF MARYLAND BALTIMORE · PI FEYRUZ VIRGILIA RASSOOL · 2008 to 2026
$51.0M
Mechanism-based approach to combine histone deacetylase inhibitors with PARP inhibitors for therapy in AMLR21CA208937 · NCI · UNIVERSITY OF MARYLAND BALTIMORE · PI RASSOOL, FEYRUZ VIRGILIA · 2017 to 2018
$369k
Mechanisms for sensitivity to PARP inhibitors in cancers involving ALT NHEJR21CA186974 · NCI · UNIVERSITY OF MARYLAND BALTIMORE · PI RASSOOL, FEYRUZ VIRGILIA · 2015 to 2016
$367k
Inhibition of Pim kinases in acute myeloid leukemiaI01BX002184 · VA · BALTIMORE VA MEDICAL CENTER · PI BAER, MARIA R · 2015 to 2018
–
BLRD VA I01 BX002184NCI NIH HHS P30 CA134274NCI NIH HHS R21 CA186974NCI NIH HHS R21 CA208937
6 · The paper itself

Abstract

Internal tandem duplications within the juxtamembrane domain of fms-like tyrosine kinase 3 (FLT3-ITD) occur in acute myeloid leukemia (AML) cells of 20-25% of patients and are associated with poor treatment outcomes. FLT3 inhibitors have been developed, but have had limited clinical efficacy due to development of resistance, highlighting the need for better understanding of the function of FLT3-ITD and how to target it more effectively using novel combination strategies. Poly (ADP-ribose) polymerase (PARP) inhibitors have shown efficacy in cancers with impaired homologous recombination (HR) due to BRCA mutations, but PARP inhibitor efficacy has not been fully explored in BRCA-proficient cancers, including AML. Recent research has connected inhibition of FLT3-ITD signaling to downregulation of numerous DNA repair proteins, including those involved in HR, and the novel combination with PARP inhibitors induces synthetic lethality in AML. Additionally, PARP inhibitor therapy may also target the highly error-prone alternative non-homologous end-joining (ALT NHEJ) DNA repair pathway in which PARP participates, thereby decreasing genomic instability and development of therapy resistance. Therefore, PARP inhibitors may be attractive therapeutic agents in combination with FLT3 inhibitors in FLT3-ITD AML.

Indexed as

Animalsfms-Like Tyrosine Kinase 3Genomic InstabilityHumansLeukemia, Myeloid, AcutePoly(ADP-ribose) Polymerase InhibitorsFLT3 protein, humanfms-Like Tyrosine Kinase 3Poly(ADP-ribose) Polymerase InhibitorsAcute myeloid leukemiaDNA repairFLT3 inhibitorsFLT3-ITDGenomic instabilityPARP inhibitors

Identifiers

PMID30953707
PMCPMC6528833
OpenAlexW2928976519

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.