Inhibition of androgen receptor transactivation function by adenovirus type 12 E1A undermines prostate cancer cell survival

Li, Dawei; Tian, Guimei; Wang, Jia; Zhao, Lisa; Co, Olivia; Underill, Zoe C.; Mymryk, Joe S.; Claessens, Frank; Dehm, Scott M.; Daaka, Yehia

doi:10.1002/pros.23689

Cited by 5 publications

(3 citation statements)

References 67 publications

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“…In vivo studies showed that injection of HAdV-A12 into mouse brain induced cancerous brain tumors [ 73 , 74 ]. Only one study [ 75 ] examined the oncolytic activity of HAdV-A. Li et al [ 75 ] concluded that recombinant HAdV-E1A12 targets androgen receptor (AR)-mediated transcription and kills prostate cancer (PC) cells.…”

Section: Oncolytic Adenoviruses—genetic Modifications To Enhance Onco...mentioning

confidence: 99%

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Oncolytic Adenoviruses Armed with Co-Stimulatory Molecules for Cancer Treatment

Gryciuk

Rogalska

Baran

et al. 2023

Cancers

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In clinical trials, adenovirus vectors (AdVs) are commonly used platforms for human gene delivery therapy. High genome capacity and flexibility in gene organization make HAdVs suitable for cloning. Recent advancements in molecular techniques have influenced the development of genetically engineered adenovirus vectors showing therapeutic potential. Increased molecular understanding of the benefits and limitations of HAdVs in preclinical research and clinical studies is a crucial point in the engineering of refined oncolytic vectors. This review presents HAdV species (A–G) used in oncotherapy. We describe the adenovirus genome organizations and modifications, the possibilities oncolytic viruses offer, and their current limitations. Ongoing and ended clinical trials based on oncolytic adenoviruses are presented. This review provides a broad overview of the current knowledge of oncolytic therapy. HAdV-based strategies targeting tumors by employing variable immune modifiers or delivering immune stimulatory factors are of great promise in the field of immune oncologyy This approach can change the face of the fight against cancer, supplying the medical tools to defeat tumors more selectively and safely.

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Section: Oncolytic Adenoviruses—genetic Modifications To Enhance Onco...mentioning

confidence: 99%

“…Only one study [ 75 ] examined the oncolytic activity of HAdV-A. Li et al [ 75 ] concluded that recombinant HAdV-E1A12 targets androgen receptor (AR)-mediated transcription and kills prostate cancer (PC) cells.…”

Section: Oncolytic Adenoviruses—genetic Modifications To Enhance Onco...mentioning

confidence: 99%

Oncolytic Adenoviruses Armed with Co-Stimulatory Molecules for Cancer Treatment

Gryciuk

Rogalska

Baran

et al. 2023

Cancers

View full text Add to dashboard Cite

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“…Previous studies have found that adenoviruses can produce at least 50 serotypes. Through the study of various serotypes, it is found that serotype 12E1A inhibits AR-mediated transcription and prostate cancer cell survival, suggesting that E1A12-targeted AR may have a potential therapeutic effect on the treatment of advanced prostate cancer with increased AR (120). In addition to its serotype affecting the development of prostate cancer, adenovirus expressing Fas ligand (FasL) can induce apoptosis in a group of prostate cancer cell lines.…”

Section: Virusmentioning

confidence: 99%

Prostate Microbiota and Prostate Cancer: A New Trend in Treatment

Che

Zhang

et al. 2021

Front. Oncol.

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Although the incidence and mortality of prostate cancer have gradually begun to decline in the past few years, it is still one of the leading causes of death from malignant tumors in the world. The occurrence and development of prostate cancer are affected by race, family history, microenvironment, and other factors. In recent decades, more and more studies have confirmed that prostate microflora in the tumor microenvironment may play an important role in the occurrence, development, and prognosis of prostate cancer. Microorganisms or their metabolites may affect the occurrence and metastasis of cancer cells or regulate anti-cancer immune surveillance. In addition, the use of tumor microenvironment bacteria in interventional targeting therapy of tumors also shows a unique advantage. In this review, we introduce the pathway of microbiota into prostate cancer, focusing on the mechanism of microorganisms in tumorigenesis and development, as well as the prospect and significance of microorganisms as tumor biomarkers and tumor prevention and treatment.

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Androgen receptor variant-driven prostate cancer II: advances in laboratory investigations

Brown

Antonarakis

et al. 2020

Prostate Cancer Prostatic Dis

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Background: The androgen receptor (AR) is a key prostate cancer drug target. Suppression of AR signaling mediated by the full-length AR (AR-FL) is the therapeutic goal of all existing AR-directed therapies. AR-targeting agents impart therapeutic benefit, but lead to AR aberrations that underlie disease progression and therapeutic resistance. Among the AR aberrations specific to castration-resistant prostate cancer (CRPC), AR variants (AR-Vs) have emerged as important indicators of disease progression and therapeutic resistance. Methods: We conducted a systemic review of the literature focusing on recent laboratory studies on AR-Vs following our last review article published in 2016. Topics ranged from measurement and detection, molecular origin, regulation, genomic function, and preclinical therapeutic targeting of AR-Vs. We provide expert opinions and perspectives on these topics. Results: Transcript sequences for 22 AR-Vs have been reported in the literature. Different AR-Vs may arise through different mechanisms, and can be regulated by splicing factors and dictated by genomic rearrangements, but a low-androgen environment is a prerequisite for generation of AR-Vs. The unique transcript structures allowed development of in-situ and in-solution measurement and detection methods, including mRNA and protein detection, in both tissue and blood specimens. AR variant-7 (AR-V7) remains the main measurement target and the most extensively characterized AR-V. Although AR-V7 co-exists with AR-FL, genomic functions mediated by AR-V7 do not require the presence of AR-FL. The distinct cistromes and transcriptional programs directed by AR-V7 and their co-regulators are consistent with genomic features of progressive disease in a low-androgen environment. Preclinical development of AR-V-directed agents currently focuses on suppression of mRNA expression and protein degradation as well as targeting of the amino-terminal domain. Conclusions: Current literature continues to support AR-Vs as biomarkers and therapeutic targets in prostate cancer. Laboratory investigations reveal both challenges and opportunities in targeting AR-Vs to overcome resistance to current AR-directed therapies.

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Inhibition of androgen receptor transactivation function by adenovirus type 12 E1A undermines prostate cancer cell survival

Abstract: Ad12 E1A inhibits AR-mediated transcription and suppresses PCa cell survival, suggesting that targeting the AR by E1A12 might have therapeutic potential for treating advanced PCa with heightened AR signaling.

Cited by 5 publications

References 67 publications

Oncolytic Adenoviruses Armed with Co-Stimulatory Molecules for Cancer Treatment

Oncolytic Adenoviruses Armed with Co-Stimulatory Molecules for Cancer Treatment

Prostate Microbiota and Prostate Cancer: A New Trend in Treatment

Androgen receptor variant-driven prostate cancer II: advances in laboratory investigations

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