Evidence map›Paper›PMID 32968206›Full record

ArticleBritish journal of cancer2020

CRISPR/Cas9 genome-wide loss-of-function screening identifies druggable cellular factors involved in sunitinib resistance in renal cell carcinoma.

Peter Makhov, Ji A Sohn, Ilya G Serebriiskii, Rushaniya Fazliyeva, Vladimir Khazak, Yanis Boumber, Robert G Uzzo, Vladimir M Kolenko

Open access · hybridAbstract read
In one paragraph

Article in British journal of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
0.9field-weighted citation impact, top 27% 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

18 citing papers in PubMed, 27 citations in OpenAlex.

  1. Review
  2. Expanding the CRISPR/Cas toolkit: applications in proteomics and theranostics.Frontiers in bioengineering and biotechnology · 2025
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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

8 authors at 1 institution in 2 countries.

Peter MakhovMolecular Therapeutics Program, Fox Chase Cancer Center, Philadelphia, PA, USA. Petr.Makhov@fccc.edu.ORCID http://orcid.org/0000-0002-8257-4782
Ji A SohnBlood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, PA, USA.
Ilya G SerebriiskiiMolecular Therapeutics Program, Fox Chase Cancer Center, Philadelphia, PA, USA.
Rushaniya FazliyevaCancer Biology Program, Fox Chase Cancer Center, Philadelphia, PA, USA.
Vladimir KhazakPriaxon Inc., Philadelphia, PA, USA.
Yanis BoumberDepartment of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA.
Robert G UzzoDivision of Urologic Oncology, Department of Surgery, Fox Chase Cancer Center, Philadelphia, PA, USA.
Vladimir M KolenkoCancer Biology Program, Fox Chase Cancer Center, Philadelphia, PA, USA.
Fox Chase Cancer Center · US

Funding

Targeting Musashi-2 (MSI2) regulation of VEGFR2 / VEGF-A in lung cancerR01CA218802 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI BOUMBER, YANIS · 2018 to 2022
$1.9M
Margret B. Einarson, Ph.D., Manager, High Throughput Screening Facility, Fox Chase Cancer CenterR50CA211479 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI EINARSON, MARGRET B · 2017 to 2021
$636k
Targeting Musashi-2 (MSI2) regulation of EGFR and HER2 in lung cancerR21CA223394 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI MAKHOV, PETR B. · 2018 to 2019
$436k
The role of cholesterol homeostasis in enzalutamide resistanceR03CA235060 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI KOLENKO, VLADIMIR M · 2020 to 2021
$187k
Novel anti-CD70-VEGF-trap fusion antibodies as a next-generation therapeutic approach for renal cancerR03CA246011 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI MAKHOV, PETR B. · 2020 to 2021
$187k
Disrupting lysosomal sequestration of sunitinib by farnesyl-transferase inhibitors as a next generation therapeutic approach for TKI resistant RCCR03CA216173 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI MAKHOV, PETR B. · 2018 to 2019
$183k
LDL cholesterol and TKI resistance in renal cell carcinomaR03CA212949 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI KOLENKO, VLADIMIR M · 2017 to 2018
$183k
NCI NIH HHS R01 CA218802NCI NIH HHS R03 CA212949NCI NIH HHS R03 CA216173NCI NIH HHS R03 CA235060NCI NIH HHS R03 CA246011NCI NIH HHS R21 CA223394NCI NIH HHS R50 CA211479U.S. Department of Defense (United States Department of Defense) KC170127U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) CA223394
6 · The paper itself

Abstract

backgroundMulti-targeted tyrosine kinase inhibitors (TKIs) are the standard of care for patients with advanced clear cell renal cell carcinoma (ccRCC). However, a significant number of ccRCC patients are primarily refractory to targeted therapeutics, showing neither disease stabilisation nor clinical benefits.

methodsWe used CRISPR/Cas9-based high-throughput loss of function (LOF) screening to identify cellular factors involved in the resistance to sunitinib. Next, we validated druggable molecular factors that are synthetically lethal with sunitinib treatment using cell and animal models of ccRCC.

resultsOur screening identified farnesyltransferase among the top hits contributing to sunitinib resistance in ccRCC. Combined treatment with farnesyltransferase inhibitor lonafarnib potently augmented the anti-tumour efficacy of sunitinib both in vitro and in vivo.

conclusionCRISPR/Cas9 LOF screening presents a promising approach to identify and target cellular factors involved in the resistance to anti-cancer therapeutics.

Indexed as

AnimalsAntineoplastic AgentsApoptosisCarcinoma, Renal CellCell Line, TumorCRISPR-Cas SystemsDibenzocycloheptenesDNA FragmentationDrug InteractionsDrug Resistance, NeoplasmDrug Therapy, CombinationEnzyme InhibitorsFarnesyltranstransferaseHigh-Throughput Screening AssaysHumansKidney NeoplasmsAntineoplastic AgentsDibenzocycloheptenesEnzyme InhibitorsFarnesyltranstransferaselonafarnibMechanistic Target of Rapamycin Complex 1PiperidinesProtein Kinase InhibitorsPyridinesRNA, Small InterferingSunitinib

Identifiers

PMID32968206
PMCPMC7723036
OpenAlexW3088399014

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.