Evidence map›Paper›PMID 39879384›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2025

Targeting AXL Inhibits the Growth and Metastasis of Prostate Cancer in Bone.

Chun-Lung Chiu, Dalin Zhang, Hongjuan Zhao, Yi Wei, Alexandra Lapat Polasko, Mikkel Thy Thomsen, Vanessa Yang, Kasie Kexin Yang, Spencer Hauck, Eric E Peterson and 9 more

Abstract read
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

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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

19 authors.

Chun-Lung ChiuDepartment of Urology, Stanford University School of Medicine, Stanford, California.ORCID 0000-0001-7514-9676
Dalin ZhangDepartment of Urology, Stanford University School of Medicine, Stanford, California.ORCID 0000-0002-6553-7373
Hongjuan ZhaoDepartment of Urology, Stanford University School of Medicine, Stanford, California.ORCID 0000-0001-6083-0370
Yi WeiDepartment of Urology, Stanford University School of Medicine, Stanford, California.ORCID 0009-0000-4883-3851
Alexandra Lapat PolaskoDepartment of Urology, Stanford University School of Medicine, Stanford, California.ORCID 0000-0002-1892-0847
Mikkel Thy ThomsenDepartment of Urology, Stanford University School of Medicine, Stanford, California.ORCID 0000-0001-6515-675X
Vanessa YangDepartment of Urology, Stanford University School of Medicine, Stanford, California.ORCID 0009-0005-9072-6685
Kasie Kexin YangDepartment of Urology, Stanford University School of Medicine, Stanford, California.ORCID 0009-0004-0908-7365
Spencer HauckDepartment of Pathology, Duke University School of Medicine, Durham, North Carolina.ORCID 0000-0003-1722-8709
Eric E PetersonDepartment of Urology, Stanford University School of Medicine, Stanford, California.ORCID 0000-0002-5006-3865
Ru M WenDepartment of Urology, Stanford University School of Medicine, Stanford, California.ORCID 0000-0002-4141-7377
Zhengyuan QiuDepartment of Urology, Stanford University School of Medicine, Stanford, California.ORCID 0009-0004-5160-6587
Eva CoreyDepartment of Urology, University of Washington, Seattle, Washington.ORCID 0000-0002-9244-3807
Yu Rebecca MiaoDepartment of Radiation Oncology, Stanford University School of Medicine, Stanford, California.ORCID 0000-0002-5848-9924
Erinn B RankinDepartment of Radiation Oncology, Stanford University School of Medicine, Stanford, California.ORCID 0000-0002-2045-2296
Donna M PeehlDepartment of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California.ORCID 0009-0003-8592-7242
Jiaoti HuangDepartment of Pathology, Duke University School of Medicine, Durham, North Carolina.ORCID 0000-0003-1195-1998
Amato J GiacciaDepartment of Radiation Oncology, Stanford University School of Medicine, Stanford, California.ORCID 0000-0002-9469-1388
James D BrooksDepartment of Urology, Stanford University School of Medicine, Stanford, California.ORCID 0000-0003-4521-7505

Funding

Translational Biology CoreP01CA257907 · NCI · STANFORD UNIVERSITY · PI Maximilian Diehn · 2022 to 2026
$12.0M
Stanford Molecular and Cellular Characterization LaboratoryU01CA196387 · NCI · STANFORD UNIVERSITY · PI BROOKS, JAMES D. · 2015 to 2020
$5.2M
The role of the RNA demethylase FTO in metabolic reprogramming of renal cell carcinomaR01CA272432 · NCI · STANFORD UNIVERSITY · PI Erinn B Rankin · 2023 to 2026
$1.8M
Multidisciplinary K12 Urologic Research at Stanford (KUReS) Career Development ProgramK12DK137162 · NIDDK · STANFORD UNIVERSITY · PI JAMES D. BROOKS, JOSEPH C LIAO · 2023 to 2026
$1.7M
Targeting AXL to overcome resistance to taxanes and platinum-based therapy in castrate resistant and neuroendocrine prostate cancerR21CA245595 · NCI · STANFORD UNIVERSITY · PI BROOKS, JAMES D. · 2020 to 2021
$406k
National Cancer Institute (NCI) RO1 CA272432NCI NIH HHS P01 CA257907NCI NIH HHS R01 CA272432NCI NIH HHS R21 CA245595NCI NIH HHS U01 CA196387NIDDK NIH HHS K12 DK137162U.S. Department of Defense (DOD) W81XWH2110195U.S. Department of Defense (DOD) W81XWH2210651
6 · The paper itself

Abstract

purposeAfter failing primary and secondary hormonal therapy, castration-resistant and neuroendocrine prostate cancer metastatic to the bone is invariably lethal, although treatment with docetaxel and carboplatin can modestly improve survival. Therefore, agents targeting biologically relevant pathways in prostate cancer and potentially synergizing with docetaxel and carboplatin in inhibiting bone metastasis growth are urgently needed. EXPERIMENTAL

designPhosphorylated (activated) AXL expression in human prostate cancer bone metastases was assessed by IHC staining. We evaluated the effects of a novel soluble AXL signaling inhibitor, sAXL (batiraxcept or AVB-S6-500), on tumor growth and lung metastases in prostate cancer patient-derived xenograft models that were implanted intratibially. After injection of LuCaP cells into the tibiae, tumors were treated with batiraxcept and docetaxel or carboplatin alone or in combination, and tumor growth was monitored by serum prostate-specific antigen or bioluminescence. Tumor burden was quantified by human-specific Ku70 staining, and metastasis to the lungs was determined using qPCR. Transcriptomic profiling, Western blotting, and immunohistochemistry were performed to identify treatment-regulated gene and protein profile changes.

resultsHigh AXL phosphorylation in human prostate cancer bone metastases correlated with shortened survival. Batiraxcept alone or in combination with docetaxel or carboplatin significantly suppressed intratibial tumor growth and suppressed metastasis to the lungs through multiple mechanisms, including repression of cancer stemness genes (CD44, ALDH1A1, TACSTD2, and ATXN1) and the PI3K, JAK, MAPK, and E2F1/NUSAP1 signaling pathways.

conclusionsOur study provides a robust preclinical rationale and mechanisms of action for using batiraxcept as a single agent or in combination with docetaxel or carboplatin to treat lethal metastatic prostate cancer.

Indexed as

Bone NeoplasmsProstatic NeoplasmsProto-Oncogene ProteinsReceptor Protein-Tyrosine KinasesAnimalsAxl Receptor Tyrosine KinaseCarboplatinCell Line, TumorCell ProliferationDocetaxelGene Expression Regulation, NeoplasticHumansLung NeoplasmsMaleMicePhosphorylationAXL protein, humanAxl Receptor Tyrosine KinaseCarboplatinDocetaxelProto-Oncogene ProteinsReceptor Protein-Tyrosine Kinases

Identifiers

PMID39879384
PMCPMC11961319

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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.