Radiotherapy-resistant prostate cancer cells escape immune checkpoint blockade through the senescence-related ataxia telangiectasia and Rad3-related protein.

Background: The majority of patients with prostate cancer (PCa) exhibit intrinsic resistance to immune checkpoint blockade (ICB) following radiotherapy (RT). This resistance is generally attributed to the limited antigen presentation of heterogeneous cells within tumors. Here, we aimed to isolate and characterize these diverse subgroups of tumor post-RT to understand the molecular mechanisms of their resistance to ICB.

Monoacylglycerol lipase blockades the senescence-associated secretory phenotype by interfering with NF-κB activation and promotes docetaxel efficacy in prostate cancer.

Metabolic reprogramming and cellular senescence greatly contribute to cancer relapse and recurrence. In aging and treated prostate, persistent accumulating senescence-associated secretory phenotype (SASP) of cancer cells often limits the overall survival of patients. Novel strategic therapy with monoacylglycerol lipase (MGLL) upregulation that counters the cellular and docetaxel induced SASP might overcome this clinical challenge in prostate cancer (PCa).

Based on PI-RADS v2.1 combining PHI and ADC values to guide prostate biopsy in patients with PSA 4-20 ng/mL.

Purpose: The study aimed to investigate the diagnostic accuracy of prostate health index (PHI) and apparent diffusion coefficient (ADC) values in predicting prostate cancer (PCa) and construct a nomogram for the prediction of PCa and clinically significant PCa (CSPCa) in Prostate Imaging-Reporting and Data System (PI-RADS) three lesions cohort.

Methods: This study prospectively enrolled 301 patients who underwent multiparametric magnetic resonance (mpMRI) and were scheduled for prostate biopsy. The receiver operating characteristic curve (ROC) was performed to estimate the diagnostic accuracy of each predictor.

P300/SP1 complex mediating elevated METTL1 regulates CDK14 mRNA stability via internal m7G modification in CRPC.

Background: N7-methylguanosine (m7G) modification is, a more common epigenetic modification in addition to m6A modification, mainly found in mRNA capsids, mRNA interiors, transfer RNA (tRNA), pri-miRNA, and ribosomal RNA (rRNA). It has been found that m7G modifications play an important role in mRNA transcription, tRNA stability, rRNA processing maturation, and miRNA biosynthesis. However, the role of m7G modifications within mRNA and its "writer" methyltransferase 1(METTL1) in tumors, particularly prostate cancer (PCa), has not been revealed.

Six-transmembrane epithelial antigen of prostate 3 (STEAP3) is a potential prognostic biomarker in clear cell renal cell carcinoma that correlates with M2 macrophage infiltration and epithelial-mesenchymal.

Background: The six-transmembrane epithelial antigen of the prostate 3 (STEAP3) is a metalloreductase, which is essential for iron uptake. Existing literature has shown that STEAP3 may perform an important role in the onset and progression of tumors. Nonetheless, a complete pan-cancer investigation of the prognostic significance and immune properties of STEAP3 is currently unavailable.

Enhancer RNA promotes resistance to radiotherapy in bone-metastatic prostate cancer by mA modification.

Prostate cancer metastasizes to the bone with the highest frequency and exhibits high resistance to Lu-prostate-specific membrane antigen (PSMA) radioligand therapy. Little is known about bone metastatic prostate cancer (mPCa) resistance to radiation. We filtered the metastatic eRNA using RNA-seq, MeRIP-seq, RT-qPCR and bioinformation.

Identification of LAT/ZAP70 characterized immune subtypes of prostate cancer.

Background: While immunotherapy has shown potent efficacy in clinical practices, patient selection to receive checkpoint blockade is still challenging in prostate cancer (PCa). LAT and ZAP70 functions in lymphocyte activation and plays a critical role in T cell receptor (TCR) signal transduction. However, PCa genomic and clinical data regarding the role of LAT and ZAP70 are limited.

Primary teratoma of the adrenal gland: a case report.

Background: Teratomas are unusual tumors derived from multiple germ layers but they usually arise from all three germ layers. Knowledge of this disease is still very limited because of its low incidence. Retroperitoneal teratomas are extremely rare neoplasms, especially adrenal teratomas, which frequently found to be large, cystic or cyst-solid lesions.

FOXA1 overexpression suppresses interferon signaling and immune response in cancer.

Androgen receptor-positive prostate cancer (PCa) and estrogen receptor-positive luminal breast cancer (BCa) are generally less responsive to immunotherapy compared with certain tumor types such as melanoma. However, the underlying mechanisms are not fully elucidated. In this study, we found that FOXA1 overexpression inversely correlated with interferon (IFN) signature and antigen presentation gene expression in PCa and BCa patients.

Functional roles of antisense enhancer RNA for promoting prostate cancer progression.

Enhancer RNA (eRNA) bi-directionally expresses from enhancer region and sense eRNA regulates adjacent mRNA in cis and in trans. However, it has remained unclear whether antisense eRNAs in different direction are functional or merely a reflection of enhancer activation. Strand-specific, ribosome-minus RNA sequencing (RNA-seq) were performed in AR positive prostate cancer cells.

Long non-coding RNA NEAT1 promotes bone metastasis of prostate cancer through N6-methyladenosine.

Background: N6-methyladenosine (m6A) is the most prevalent messenger RNA modification in mammalian cells. However, the disease relevant function of m6A on specific oncogenic long non-coding RNAs (ncRNAs) is not well understood.

Methods: We analyzed the m6A status using patients samples and bone metastatic PDXs.

Impact of Long Non-coding RNAs Associated With Microenvironment on Survival for Bladder Cancer Patients.

Background: Cumulative evidence from several tumor studies, including bladder cancer, emphasizes the importance of the tumor microenvironment (TME) in tumorigenesis, development, and metastasis, which can be regulated by long non-coding RNAs (lncRNAs). This study aims to identify bladder cancer (BC) microenvironment-associated lncRNAs for their prognostic value predicting the survival of BC patients.

Methods: The data of BC patients regarding lncRNA expression and corresponding clinical characteristics were obtained from The Cancer Genome Atlas (TCGA).

Posttranslational regulation of androgen dependent and independent androgen receptor activities in prostate cancer.

Prostate cancer (PCa) is the most commonly diagnosed cancer among men in western countries. Androgen receptor (AR) signaling plays key roles in the development of PCa. Androgen deprivation therapy (ADT) remains the standard therapy for advanced PCa.

Aberrant activation of super enhancer and choline metabolism drive antiandrogen therapy resistance in prostate cancer.

Next generation antiandrogens such as enzalutamide (Enz) are effective initially for the treatment of castration-resistant prostate cancer (CRPC). However, the disease often relapses and the underlying mechanisms remain elusive. By performing H3-lysine-27 acetylation (H3K27ac) ChIP-seq in Enz-resistant CRPC cells, we identified a group of super enhancers (SEs) that are abnormally activated in Enz-resistant CRPC cells and associated with enhanced transcription of a subset of tumor promoting genes such as CHPT1, which catalyzes phosphatidylcholine (PtdCho) synthesis and regulates choline metabolism.

Correction: Neurotensin and its receptors mediate neuroendocrine transdifferentiation in prostate cancer.

A correction to this paper has been published and can be accessed via a link at the top of the paper.

Neurotensin and its receptors mediate neuroendocrine transdifferentiation in prostate cancer.

Castration-resistant prostate cancer (CRPC) with neuroendocrine differentiation (NED) is a lethal disease for which effective therapies are urgently needed. The mechanism underlying development of CRPC with NED, however, remains largely uncharacterized. In this study, we explored and characterized the functional role of neurotensin (NTS) in cell line and animal models of CRPC with NED.

ADT with antiandrogens in prostate cancer induces adverse effect of increasing resistance, neuroendocrine differentiation and tumor metastasis.

Prostate cancer (PCa) is the most common cancer and the 2nd leading cause of cancer-related deaths among men in the United States. Androgen-deprivation-therapy (ADT) with antiandrogens to target the androgens/androgen receptor (AR) signals remains the standard therapy for advanced PCa. However, most of the PCa patients who received ADT with antiandrogens, including the recently developed Enzalutamide (Enz) that might extend PCa patients survival an extra 4.

Targeting estrogen/estrogen receptor alpha enhances Bacillus Calmette-Guérin efficacy in bladder cancer.

Recent studies showed the potential linkage of estrogen/estrogen receptor signaling with bladder tumorigenesis, yet detailed mechanisms remain elusive. Here we found a new potential therapy with the combination of Bacillus Calmette-Guerin (BCG) and the anti-estrogen ICI 182,780 led to better suppression of bladder cancer (BCa) than BCG alone. Mechanism dissection found ICI 182,780 could promote BCG attachment/internalization to the BCa cells through increased integrin-α5β1 expression and IL-6 release, which may enhance BCG-induced suppression of BCa cell growth via recruiting more monocytes/macrophages to BCa cells and increased TNF-α release.

ASC-J9(®), and not Casodex or Enzalutamide, suppresses prostate cancer stem/progenitor cell invasion via altering the EZH2-STAT3 signals.

Early studies suggested that prostate cancer (PCa) stem/progenitor (S/P) cells might play key roles to promote the tumor initiation and metastasis. Yet their linkage to the failure of androgen deprivation therapy (ADT), however, remains unclear. Here we demonstrated that the ADT with anti-androgens Casodex (also known as Bicalutamide) and Enzalutamide (also known as MDV3100), but not the newly identified AR degradation enhancer, ASC-J9(®), increased PCa S/P population, which might then lead to enhance the PCa cell invasion.

Targeting fatty acid synthase with ASC-J9 suppresses proliferation and invasion of prostate cancer cells.

Fatty acid synthase (FASN) is the key enzyme for the control of fatty acid synthesis that contributes significantly to the prostate cancer (PCa) progression. It was reported that androgens were able to induce FASN expression in PCa, and addition of the anti-androgen Casodex might suppress the androgen-induced FASN expression. However, here we found androgen-deprivation-therapy (ADT) with anti-androgens Bicalutamide (Casodex) or Enzalutamide (MDV3100) had little effect to suppress FASN expression and FASN-mediated cell growth and invasion during the castration resistant stage when the androgen concentration is 1 nM DHT (dihydrotestosterone).

BM-MSCs promote prostate cancer progression via the conversion of normal fibroblasts to cancer-associated fibroblasts.

Recent studies have suggested that prostate cancer (PCa) is able to recruit bone marrow derived mesenchymal stem cells (BM-MSCs) to promote metastasis. The detailed mechanisms, especially the involvement of stromal cells, remain unclear. We found that the recruited BM-MSCs might be able to convert the normal fibroblasts to more cancer associated fibroblast (CAF)-like characteristics via alteration of secreted TGFβ-1.

What is the next generation therapeutic strategy for castration-resistant prostate cancer.

Prostate cancer (PCa) is one of the most common cancers in the world. Since androgen receptor (AR) signal plays key roles in the PCa progression, targeting androgens via the current androgen deprivation therapy (ADT) is the main therapeutic strategy for advanced PCa. However, most patients who receive ADT, including the second generation anti-androgens enzalutamide (also known as MDV3100) may finally develop the castration (or anti-androgen) resistance after 12-24 months treatment.

Stromal androgen receptor roles in the development of normal prostate, benign prostate hyperplasia, and prostate cancer.

The prostate is an androgen-sensitive organ that needs proper androgen/androgen receptor (AR) signals for normal development. The progression of prostate diseases, including benign prostate hyperplasia (BPH) and prostate cancer (PCa), also needs proper androgen/AR signals. Tissue recombination studies report that stromal, but not epithelial, AR plays more critical roles via the mesenchymal-epithelial interactions to influence the early process of prostate development.