Evidence map›Paper›PMID 34088900›Full record

ArticleCell death & disease2021

Predicting ROR1/BCL2 combination targeted therapy of small cell carcinoma of the lung.

Walter Z Wang, Konstantin Shilo, Joseph M Amann, Alyssa Shulman, Mohammad Hojjat-Farsangi, Håkan Mellstedt, Johan Schultz, Carlo M Croce, David P Carbone

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.6field-weighted citation impact, top 13% 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

9 citing papers in PubMed, 20 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Review
  5. Article
  6. Review
  7. Article
  8. Review
  9. 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

9 authors at 3 institutions in 2 countries.

Walter Z WangDepartment of Internal Medicine, Division of Medical Oncology, The Ohio State University, Columbus, OH, 43210, USA. walter.wang@osumc.edu.ORCID 0000-0003-1054-4688
Konstantin ShiloDepartment of Pathology, The Ohio State University, Columbus, OH, 43210, USA.
Joseph M AmannDepartment of Internal Medicine, Division of Medical Oncology, The Ohio State University, Columbus, OH, 43210, USA.
Alyssa ShulmanDepartment of Internal Medicine, Division of Medical Oncology, The Ohio State University, Columbus, OH, 43210, USA.
Mohammad Hojjat-FarsangiDepartment of Oncology-Pathology, Karolinska Institutet, 17177, Stockholm, Sweden.ORCID 0000-0002-0589-5523
Håkan MellstedtDepartment of Oncology-Pathology, Karolinska Institutet, 17177, Stockholm, Sweden.
Johan SchultzKancera AB, Banvaktsvägen 22, 17148, Solna, Sweden.
Carlo M CroceThe Comprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA.
David P CarboneDepartment of Internal Medicine, Division of Medical Oncology, The Ohio State University, Columbus, OH, 43210, USA. david.carbone@osumc.edu.ORCID 0000-0003-3002-1921
The Ohio State University · USKarolinska Institutet · SEProcera Networks (Sweden) · SE

Funding

Cancer Gene Discovery to Identify Targetable TargetsR35CA197706 · NCI · OHIO STATE UNIVERSITY · PI CROCE, CARLO M · 2015 to 2021
$6.4M
NCI NIH HHS R35 CA197706
6 · The paper itself

Abstract

Small cell lung cancer (SCLC) remains a deadly form of cancer, with a 5-year survival rate of less than 10 percent, necessitating novel therapies. Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is an oncofetal protein that is emerging as a therapeutic target and is co-expressed with BCL2 in multiple tumor types due to microRNA coregulation. We hypothesize that ROR1-targeted therapy is effective in small cell lung cancer and synergizes with therapeutic BCL2 inhibition. Tissue microarrays (TMAs) and formalin-fixed paraffin-embedded (FFPE) SCLC patient samples were utilized to determine the prevalence of ROR1 and BCL2 expression in SCLC. Eight SCLC-derived cell lines were used to determine the antitumor activity of a small molecule ROR1 inhibitor (KAN0441571C) alone and in combination with the BCL2 inhibitor venetoclax. The Chou-Talalay method was utilized to determine synergy with the drug combination. ROR1 and BCL2 protein expression was identified in 93% (52/56) and 86% (48/56) of SCLC patient samples, respectively. Similarly, ROR1 and BCL2 were shown by qRT-PCR to have elevated expression in 79% (22/28) and 100% (28/28) of SCLC patient samples, respectively. KAN0441571C displayed efficacy in 8 SCLC cell lines, with an IC50 of 500 nM or less. Synergy as defined by a combination index of <1 via the Chou-Talalay method between KAN0441571C and venetoclax was demonstrated in 8 SCLC cell lines. We have shown that ROR1 inhibition is synergistic with BCL2 inhibition in SCLC models and shows promise as a novel therapeutic target in SCLC.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsBridged Bicyclo Compounds, HeterocyclicCell Line, TumorDrug SynergismHumansLung NeoplasmsMolecular Targeted TherapyProtein Kinase InhibitorsProto-Oncogene Proteins c-bcl-2Receptor Tyrosine Kinase-like Orphan ReceptorsSmall Cell Lung CarcinomaSulfonamidesSurvival AnalysisBCL2 protein, humanBridged Bicyclo Compounds, HeterocyclicProtein Kinase InhibitorsProto-Oncogene Proteins c-bcl-2Receptor Tyrosine Kinase-like Orphan ReceptorsROR1 protein, humanSulfonamidesvenetoclax

Identifiers

PMID34088900
PMCPMC8178315
OpenAlexW3165440156

What OpenQuestion 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 OpenQuestion graph.