Evidence map›Paper›PMID 34680353›Full record

ReviewCancers2021

Second-Generation Jak2 Inhibitors for Advanced Prostate Cancer: Are We Ready for Clinical Development?

Paul Beinhoff, Lavannya Sabharwal, Vindhya Udhane, Cristina Maranto, Peter S LaViolette, Kenneth M Jacobsohn, Susan Tsai, Kenneth A Iczkowski, Liang Wang, William A Hall and 3 more

Open access · goldAbstract readReview
In one paragraph

Review in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.8field-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

13 citing papers in PubMed, 22 citations in OpenAlex.

  1. Article
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  6. A deep learning framework forNational science review · 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

13 authors at 2 institutions in 1 country.

Paul BeinhoffDepartment of Pathology, Medical College of Wisconsin Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA.ORCID 0000-0001-6040-9236
Lavannya SabharwalDepartment of Pathology, Medical College of Wisconsin Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Vindhya UdhaneDepartment of Pathology, Medical College of Wisconsin Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Cristina MarantoDepartment of Pathology, Medical College of Wisconsin Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Peter S LaVioletteProstate Cancer Center of Excellence at the Medical College of Wisconsin Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Kenneth M JacobsohnProstate Cancer Center of Excellence at the Medical College of Wisconsin Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Susan TsaiDepartment of Surgery, Medical College of Wisconsin Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Kenneth A IczkowskiDepartment of Pathology, Medical College of Wisconsin Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Liang WangProstate Cancer Center of Excellence at the Medical College of Wisconsin Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA.ORCID 0000-0002-9364-8572
William A HallProstate Cancer Center of Excellence at the Medical College of Wisconsin Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Scott M DehmMasonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.
Deepak KilariProstate Cancer Center of Excellence at the Medical College of Wisconsin Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Marja T NevalainenDepartment of Pathology, Medical College of Wisconsin Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Medical College of Wisconsin · USUniversity of Minnesota · US

Funding

Cell free nucleic acid-based biomarkers in advanced prostate cancerR01CA212097 · NCI · MEDICAL COLLEGE OF WISCONSIN · PI KOHLI, MANISH, WANG, LIANG · 2017 to 2022
$3.1M
NCI NIH HHS R01 CA212097
6 · The paper itself

Abstract

Androgen deprivation therapy (ADT) for metastatic and high-risk prostate cancer (PC) inhibits growth pathways driven by the androgen receptor (AR). Over time, ADT leads to the emergence of lethal castrate-resistant PC (CRPC), which is consistently caused by an acquired ability of tumors to re-activate AR. This has led to the development of second-generation anti-androgens that more effectively antagonize AR, such as enzalutamide (ENZ). However, the resistance of CRPC to ENZ develops rapidly. Studies utilizing preclinical models of PC have established that inhibition of the Jak2-Stat5 signaling leads to extensive PC cell apoptosis and decreased tumor growth. In large clinical cohorts, Jak2-Stat5 activity predicts PC progression and recurrence. Recently, Jak2-Stat5 signaling was demonstrated to induce ENZ-resistant PC growth in preclinical PC models, further emphasizing the importance of Jak2-Stat5 for therapeutic targeting for advanced PC. The discovery of the Jak2V617F somatic mutation in myeloproliferative disorders triggered the rapid development of Jak1/2-specific inhibitors for a variety of myeloproliferative and auto-immune disorders as well as hematological malignancies. Here, we review Jak2 inhibitors targeting the mutated Jak2V617F vs. wild type (WT)-Jak2 that are currently in the development pipeline. Among these 35 compounds with documented Jak2 inhibitory activity, those with potency against WT-Jak2 hold strong potential for advanced PC therapy.

Indexed as

anti-androgen resistant prostate cancercastrate-resistant prostate cancer (CRPC)Janus kinase 2 (Jak2)prostate cancer (PC)signal transducer and activator of transcription (Stat)solid tumors

Identifiers

PMID34680353
PMCPMC8533841
OpenAlexW3205618742

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.