Evidence map›Paper›PMID 41531487›Full record

ArticleFASEB bioAdvances2026

Unlocking the Power of CXCR2 Inhibition to Overcome Gemcitabine Resistance in Pancreatic Cancer.

Caitlin Molczyk, Reegan Sturgeon, Sugandha Saxena, Esther Johnson, Rakesh Bhatia, Namita Bhyravbhatla, Sushil Kumar, Surinder K Batra, Rakesh K Singh

Abstract read
In one paragraph

Article in FASEB bioAdvances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Caitlin MolczykDepartment of Pathology and Microbiology Nebraska Medical Center Omaha Nebraska USA.
Reegan SturgeonDepartment of Pathology and Microbiology Nebraska Medical Center Omaha Nebraska USA.
Sugandha SaxenaDepartment of Pathology and Microbiology Nebraska Medical Center Omaha Nebraska USA.
Esther JohnsonDepartment of Biochemistry and Molecular Biology University of Nebraska Medical Center Omaha Nebraska USA.
Rakesh BhatiaDepartment of Biochemistry and Molecular Biology University of Nebraska Medical Center Omaha Nebraska USA.
Namita BhyravbhatlaDepartment of Biochemistry and Molecular Biology University of Nebraska Medical Center Omaha Nebraska USA.
Sushil KumarDepartment of Biochemistry and Molecular Biology University of Nebraska Medical Center Omaha Nebraska USA.
Surinder K BatraDepartment of Biochemistry and Molecular Biology University of Nebraska Medical Center Omaha Nebraska USA.
Rakesh K SinghDepartment of Pathology and Microbiology Nebraska Medical Center Omaha Nebraska USA.ORCID https://orcid.org/0000-0002-1317-3520

Funding

UNMC/EPPLEY CANCER CENTER SUPPORT GRANTP30CA036727 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI James Eudy · 1985 to 2026
$55.0M
CHEMICAL CARCINOGENESIS &CANCER BIOLOGYT32CA009476 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI Jennifer D. Black · 1988 to 2026
$6.2M
Targeting CXCR2 axis in Pancreatic CancerR01CA228524 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BATRA, SURINDER K., SINGH, RAKESH K · 2018 to 2022
$2.0M
NCI NIH HHS P30 CA036727NCI NIH HHS R01 CA228524NCI NIH HHS T32 CA009476
6 · The paper itself

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related mortality, characterized by intrinsic resistance to conventional therapies and limited effective treatment options. In this study, we investigated the role of the CXCR2 axis in PDAC therapy resistance. CXCR2, a chemokine receptor, is actively involved in inflammation, tumor angiogenesis, and metastasis. Our working hypothesis is that CXCR2 contributes to PDAC chemotherapy resistance. To test this, we generated gemcitabine-resistant (GemR) lines using T3M4 and CD18/HPAF (CD18) cell lines. Baseline expression of CXCL1, CXCL5, and CXCL8 ligands was higher in GemR cells compared to parental cells. Upon gemcitabine treatment, parental cells exhibited a greater increase in CXCL1 and CXCL8 expression than GemR cells. Further analysis in T3M4 cells revealed a dose- and time-dependent increase in CXCL1 and CXCL8 expression following gemcitabine exposure. Next, we assessed whether targeting CXCR2 could enhance the therapeutic response. We treated parental and GemR cell lines with gemcitabine in combination with a CXCR2 antagonist, Navarixin. Notably, lower concentrations of gemcitabine combined with Navarixin were more effective than higher concentrations of gemcitabine alone in GemR cell lines. In both parental and GemR xenograft models, combination therapy with Navarixin and gemcitabine demonstrated superior antitumor and antimetastatic activity compared to either treatment alone. In conclusion, these findings highlight the critical role of the CXCR2 axis in PDAC therapy resistance. Targeting CXCR2 enhances gemcitabine efficacy, offering a potential therapeutic strategy to overcome resistance in PDAC.

Indexed as

CXCR2metastasispancreatic cancertherapy resistance

Identifiers

PMID41531487
PMCPMC12793072

What OpenQuestion holds

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Registered trials

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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.