Evidence map›Paper›PMID 37947652›Full record

ArticleCells2023

Development of Bexarotene Analogs for Treating Cutaneous T-Cell Lymphomas.

Ankedo Warda, Lech J P Staniszewski, Zhela Sabir, Sarah Livingston, Michael Sausedo, Sabeeha Reshi, Eyal Ron, Michael T Applegate, Dena Haddad, Madleen Khamisi and 3 more

Open access · goldAbstract read
In one paragraph

Article in Cells, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
2.9field-weighted citation impact, top 9% 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

4 citing papers in PubMed, 10 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
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

13 authors at 2 institutions in 1 country.

Ankedo WardaSchool of Mathematical and Natural Sciences, Arizona State University, Glendale, AZ 85306, USA.
Lech J P StaniszewskiSchool of Mathematical and Natural Sciences, Arizona State University, Glendale, AZ 85306, USA.
Zhela SabirSchool of Mathematical and Natural Sciences, Arizona State University, Glendale, AZ 85306, USA.
Sarah LivingstonSchool of Mathematical and Natural Sciences, Arizona State University, Glendale, AZ 85306, USA.
Michael SausedoSchool of Mathematical and Natural Sciences, Arizona State University, Glendale, AZ 85306, USA.
Sabeeha ReshiSchool of Mathematical and Natural Sciences, Arizona State University, Glendale, AZ 85306, USA.
Eyal RonCollege of Medicine, University of Arizona, Phoenix, AZ 85004, USA.
Michael T ApplegateSchool of Mathematical and Natural Sciences, Arizona State University, Glendale, AZ 85306, USA.
Dena HaddadSchool of Mathematical and Natural Sciences, Arizona State University, Glendale, AZ 85306, USA.
Madleen KhamisiSchool of Mathematical and Natural Sciences, Arizona State University, Glendale, AZ 85306, USA.
Pamela A MarshallSchool of Mathematical and Natural Sciences, Arizona State University, Glendale, AZ 85306, USA.ORCID 0000-0002-3530-4368
Carl E WagnerSchool of Mathematical and Natural Sciences, Arizona State University, Glendale, AZ 85306, USA.
Peter W JurutkaSchool of Mathematical and Natural Sciences, Arizona State University, Glendale, AZ 85306, USA.ORCID 0000-0002-4950-9161
Arizona State University · USUniversity of Arizona · US

Funding

Assessing Novel Rexinoids Developed by Comparative Bioresponse Analysis in an Innovative Mouse Model of Cutaneous T Cell LymphomaR15CA249617 · NCI · ARIZONA STATE UNIVERSITY-TEMPE CAMPUS · PI JURUTKA, PETER W, WAGNER, CARL EDWARD · 2020 to 2020
$484k
Modeling, Synthesis, and Biological Evaluation of Potential RXT Selective AgonistR15CA139364 · NCI · ARIZONA STATE UNIVERSITY-TEMPE CAMPUS · PI WAGNER, CARL EDWARD · 2011 to 2011
$458k
NCI NIH HHS R15 CA139364NCI NIH HHS R15 CA249617NIH HHS R15CA139364 and R15CA249617
6 · The paper itself

Abstract

Bexarotene, a drug approved for treatment of cutaneous T-cell lymphoma (CTCL), is classified as a rexinoid by its ability to act as a retinoid X receptor (RXR) agonist with high specificity. Rexinoids are capable of inducing RXR homodimerization leading to the induction of apoptosis and inhibition of proliferation in human cancers. Numerous studies have shown that bexarotene is effective in reducing viability and proliferation in CTCL cell lines. However, many treated patients present with cutaneous toxicity, hypothyroidism, and hyperlipidemia due to crossover activity with retinoic acid receptor (RAR), thyroid hormone receptor (TR), and liver X receptor (LXR) signaling, respectively. In this study, 10 novel analogs and three standard compounds were evaluated side-by-side with bexarotene for their ability to drive RXR homodimerization and subsequent binding to the RXR response element (RXRE). In addition, these analogs were assessed for proliferation inhibition of CTCL cells, cytotoxicity, and mutagenicity. Furthermore, the most effective analogs were analyzed via qPCR to determine efficacy in modulating expression of two critical tumor suppressor genes, ATF3 and EGR3. Our results suggest that these new compounds may possess similar or enhanced therapeutic potential since they display enhanced RXR activation with equivalent or greater reduction in CTCL cell proliferation, as well as the ability to induce ATF3 and EGR3. This work broadens our understanding of RXR-ligand relationships and permits development of possibly more efficacious pharmaceutical drugs. Modifications of RXR agonists can yield agents with enhanced biological selectivity and potency when compared to the parent compound, potentially leading to improved patient outcomes.

Indexed as

Lymphoma, T-Cell, CutaneousSkin NeoplasmsBexaroteneHumansRetinoid X ReceptorsTetrahydronaphthalenesBexaroteneRetinoid X ReceptorsTetrahydronaphthalenescancercutaneous T-cell lymphomarexinoidsRXRSAR

Identifiers

PMID37947652
PMCPMC10647404
OpenAlexW4388333616

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.