Evidence map›Paper›PMID 41957424›Full record

ArticleNPJ precision oncology2026

Integrative molecular analyses of lineage identity and morphology in aggressive variant prostate cancer.

Chennan Li, JuanJuan Yin, Melissa L Abel, Dana S Vargas Solivan, Kinjal Bhadresha, Sumeyra Kartal, Samantha Nichols, Kanak Parmar, Joseph Twohig, Tri M Truong and 5 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in NPJ precision oncology, 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

15 authors.

Chennan Li *Genitourinary Malignancies Branch, National Cancer Institute, Bethesda, MD, USA.
JuanJuan Yin *Genitourinary Malignancies Branch, National Cancer Institute, Bethesda, MD, USA.
Melissa L Abel *Genitourinary Malignancies Branch, National Cancer Institute, Bethesda, MD, USA.
Dana S Vargas SolivanGenitourinary Malignancies Branch, National Cancer Institute, Bethesda, MD, USA.
Kinjal BhadreshaGenitourinary Malignancies Branch, National Cancer Institute, Bethesda, MD, USA.
Sumeyra KartalGenitourinary Malignancies Branch, National Cancer Institute, Bethesda, MD, USA.
Samantha NicholsDevelopmental Therapeutics Branch, National Cancer Institute, Bethesda, MD, USA.
Kanak ParmarDevelopmental Therapeutics Branch, National Cancer Institute, Bethesda, MD, USA.
Joseph TwohigGenitourinary Malignancies Branch, National Cancer Institute, Bethesda, MD, USA.
Tri M TruongGenitourinary Malignancies Branch, National Cancer Institute, Bethesda, MD, USA.
Cindy H ChauGenitourinary Malignancies Branch, National Cancer Institute, Bethesda, MD, USA.
Kathleen KellyLaboratory of Genitourinary Cancer Pathogenesis, National Cancer Institute, Bethesda, MD, USA.
William D FiggGenitourinary Malignancies Branch, National Cancer Institute, Bethesda, MD, USA.
Anish ThomasDevelopmental Therapeutics Branch, National Cancer Institute, Bethesda, MD, USA.
Adam G SowalskyGenitourinary Malignancies Branch, National Cancer Institute, Bethesda, MD, USA. adam.sowalsky@nih.gov.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Aggressive variant prostate cancer (AVPC) is a lethal subtype of prostate cancer characterized by androgen independence, resistance to chemotherapy, and neuroendocrine features that can emerge de novo or via transformation after a prior diagnosis of adenocarcinoma. The poor clinical outcomes in patients with AVPC are associated with its profound molecular heterogeneity. In this study, we analyzed 23 AVPC cases using clinicogenomic and transcriptomic profiling. Transformed AVPC exhibited shorter overall survival than de novo AVPC (11.8 vs. 26.0 months). Integrative analyses identified regulators of neuronal processes in subsets of cases with neuroendocrine lineage programs, delineating a spectrum of lineage identity and morphology. To facilitate mechanistic and pharmacologic studies, we established NCI-LYM-1, a patient-derived organoid/PDX from a lymph node metastasis that faithfully recapitulates the donor tumor's molecular and phenotypic features. Genomic profiling identified biallelic inactivation of PTEN, TP53, RB1, and BRCA2 as potential drivers. These alterations were clonally concordant with circulating tumor DNA from the donor. Pathway and perturbation analyses suggested that NCI-LYM-1 harbored a strong dependency on apoptotic pathways, which was confirmed by in vitro organoid testing with BCL-2/BCL-xL and MCL-1 inhibitors. Overall, NCI-LYM-1 recapitulates the clinical aggressiveness and heterogeneity of AVPC, providing a tractable platform to identify novel precision therapies.

Identifiers

PMID41957424
PMCPMC13247060

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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.