Evidence map›Paper›PMID 38229228›Full record

ArticleMolecular pharmaceutics2024

Overcoming Resistance in Prostate Cancer Therapy Using a DZ-Simvastatin Conjugate.

Yan Ou, Gina Chia-Yi Chu, Ji Lyu, Liyuan Yin, Adrian Lim, Ning Zhai, Xiaojiang Cui, Michael S Lewis, Mouad Edderkaoui, Stephen J Pandol and 2 more

Open access · greenAbstract read
In one paragraph

Article in Molecular pharmaceutics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.3field-weighted citation impact, top 45% 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

3 citing papers in PubMed, 1 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
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

12 authors at 1 institution in 1 country.

Yan OuDepartment of Medicine, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, California 90048, United States.
Gina Chia-Yi ChuDepartment of Medicine, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, California 90048, United States.
Ji LyuDepartment of Medicine, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, California 90048, United States.
Liyuan YinDepartment of Medicine, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, California 90048, United States.
Adrian LimDepartment of Medicine, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, California 90048, United States.
Ning ZhaiDepartment of Medicine, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, California 90048, United States.
Xiaojiang CuiDepartment of Surgery, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, California 90048, United States.
Michael S LewisDepartment of Pathology, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, California 90048, United States.
Mouad EdderkaouiDepartment of Medicine, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, California 90048, United States.
Stephen J PandolDepartment of Medicine, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, California 90048, United States.
Ruoxiang WangDepartment of Medicine, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, California 90048, United States.
Yi ZhangDepartment of Biomedical Sciences, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, California 90048, United States.ORCID 0000-0001-8151-9397
Cedars-Sinai Medical Center · US

Funding

UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1M
The Role of FOXCI in Basal-like Breast CancerR01CA151610 · NCI · SAINT JOHN'S CANCER INSTITUTE · PI CUI, XIAOJIANG · 2011 to 2022
$3.8M
ROS Targeted Therapy for Lethal Prostate CancerR21CA256419 · NCI · CEDARS-SINAI MEDICAL CENTER · PI WANG, RUOXIANG, ZHANG, YI · 2021 to 2022
$425k
Crosslinking-based targeted therapy for triple-negative breast cancerR21CA280458 · NCI · ARIZONA STATE UNIVERSITY-TEMPE CAMPUS · PI CHEN, SHENGXI, CUI, XIAOJIANG · 2023 to 2024
$418k
NCATS NIH HHS UL1 TR001881NCI NIH HHS R01 CA151610NCI NIH HHS R21 CA256419NCI NIH HHS R21 CA280458
6 · The paper itself

Abstract

Prostate cancer (PC), particularly its metastatic castration-resistant form (mCRPC), is a leading cause of cancer-related deaths among men in the Western world. Traditional systemic treatments, including hormonal therapy and chemotherapy, offer limited effectiveness due to tumors' inherent resistance to these therapies. Moreover, they often come with significant side effects. We have developed a delivery method using a tumor-cell-specific heptamethine carbocyanine dye (DZ) designed to transport therapeutic agents directly to tumor cells. This research evaluated simvastatin (SIM) as the antitumor payload because of its demonstrated chemopreventive effects on human cancers and its well-documented safety profile. We designed and synthesized a DZ-SIM conjugate for tumor cell targeting. PC cell lines and xenograft tumor models were used to assess tumor-cell targeting specificity and killing activity and to investigate the corresponding mechanisms. DZ-SIM treatment effectively killed PC cells regardless of their androgen receptor status or inherent therapeutic resistance. The conjugate targeted and suppressed xenograft tumor formation without harming normal cells of the host. In cancer cells, DZ-SIM was enriched in subcellular organelles, including mitochondria, where the conjugate formed adducts with multiple proteins and caused the loss of transmembrane potential, promoting cell death. The DZ-SIM specifically targets PC cells and their mitochondria, resulting in a loss of mitochondrial function and cell death. With a unique subcellular targeting strategy, the conjugate holds the potential to outperform existing chemotherapeutic drugs. It presents a novel strategy to circumvent therapeutic resistance, offering a more potent treatment for mCRPC.

Indexed as

Prostatic Neoplasms, Castration-ResistantSimvastatinCarbocyaninesCell Line, TumorHumansMaleProstateCarbocyaninesSimvastatinconjugateheptamethine carbocyanine dyeprostate cancersimvastatintargeted therapy

Identifiers

PMID38229228
PMCPMC11025579
OpenAlexW4390954255

What OpenQuestion holds

Textmetadata
LicenceTDM
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.