Evidence map›Paper›PMID 38263737›Full record

ArticleCell cycle (Georgetown, Tex.)2024

Impact of sunitinib resistance on clear cell renal cell carcinoma therapeutic sensitivity

Susmita Ghosh, Mamatha Garige, Patrick R Haggerty, Alexis Norris, Chao-Kai Chou, Wells W Wu, Rong-Fong Shen, Carole Sourbier

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

Article in Cell cycle (Georgetown, Tex.), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.2field-weighted citation impact, top 23% 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

6 citing papers in PubMed, 5 citations in OpenAlex.

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  4. Review
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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 3 institutions in 1 country.

Susmita GhoshDivision of Biotechnology Review and Research 1, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.
Mamatha GarigeDivision of Biotechnology Review and Research 1, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.
Patrick R HaggertyDivision of Biotechnology Review and Research 1, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.
Alexis NorrisDivision of Animal Bioengineering and Cellular Therapies, Office of New Animal Drug Evaluation, Center for Veterinary Medicine, U.S. Food and Drug Administration, Rockville, MD, USA.
Chao-Kai ChouFacility for Biotechnology Resources, Center for Biologicals Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.
Wells W WuFacility for Biotechnology Resources, Center for Biologicals Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.
Rong-Fong ShenFacility for Biotechnology Resources, Center for Biologicals Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.
Carole SourbierDivision of Biotechnology Review and Research 1, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.ORCID 0000-0002-4853-7662
United States Food and Drug Administration · USCenter for Biologics Evaluation and Research · USCenter for Veterinary Medicine · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Sunitinib resistance creates a major clinical challenge for the treatment of advanced clear cell renal cell carcinoma (ccRCC) and functional and metabolic changes linked to sunitinib resistance are not fully understood. We sought to characterize the molecular and metabolic changes induced by the development of sunitinib resistance in ccRCC by developing and characterizing two human ccRCC cell lines resistant to sunitinib. Consistent with the literature, sunitinib-resistant ccRCC cell lines presented an aberrant overexpression of Axl and PD-L1, as well as a metabolic rewiring characterized by enhanced OXPHOS and glutamine metabolism. Therapeutic challenges of sunitinib-resistant ccRCC cell lines in vitro using small molecule inhibitors targeting Axl, AMPK and p38, as well as using PD-L1 blocking therapeutic antibodies, showed limited CTL-mediated cytotoxicity in a co-culture model. However, the AMPK activator metformin appears to sensitize the effect of PD-L1 blocking therapeutic antibodies and to enhance CTLs' cytotoxic effects on ccRCC cells. These effects were not broadly observed with the Axl and the p38 inhibitors. Taken together, these data suggest that targeting certain pathways aberrantly activated by sunitinib resistance such as the AMPK/PDL1 axis might sensitize ccRCC to immunotherapies as a second-line therapeutic approach.

Indexed as

Carcinoma, Renal CellKidney NeoplasmsAMP-Activated Protein KinasesB7-H1 AntigenCell Line, TumorDrug Resistance, NeoplasmHumansSunitinibAMP-Activated Protein KinasesB7-H1 AntigenSunitinibAxlmetforminOXPHOSPD-L1RCCSunitinib

Identifiers

PMID38263737
PMCPMC11005810
OpenAlexW4391173051

What OpenQuestion holds

Textmetadata
LicenceCC0
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.