ADORA2A-driven proline synthesis triggers epigenetic reprogramming in neuroendocrine prostate and lung cancers.

Cell lineage plasticity is one of the major causes for the failure of targeted therapies in various cancers. However, the driver and actionable drug targets in promoting cancer cell lineage plasticity are scarcely identified. Here, we found that a G protein-coupled receptor, ADORA2A, is specifically upregulated during neuroendocrine differentiation, a common form of lineage plasticity in prostate cancer and lung cancer following targeted therapies.

Transcriptomic signature defines two subtypes of locally advanced PCa with distinct neoadjuvant therapy benefits.

Background: Patients with locally advanced prostate cancer (LAPCa) received docetaxel-based neoadjuvant chemo-hormonal therapy (NCHT) had better clinical outcomes after surgery compared to neoadjuvant hormonal therapy (NHT) groups, but not all patients experienced favorable clinical outcomes with NCHT, raising the necessity for potential biomarker assessment. The transcriptomic profiling offers a unique opportunity to interrogate the accurate response to NCHT and NHT treatment and to identify the predictive biomarkers for neoadjuvant therapy.

Methods: The whole transcriptomic profiling was performed on baseline biopsies and surgical tissue specimens from 64 patients with LAPCa at Renji Hospital between 2014 and 2018.

The prognostic nomogram for PSA-incongruent low-risk prostate cancer treated by radical prostatectomy.

Objective: To establish a prognostic nomogram for PSA-incongruent low-risk prostate cancer (PCa) patients (Gleason score 6 and clinical stage T2a) at diagnosis and treated with radical prostatectomy (RP), based on clinical and pathological metrics.

Methods: In total, 217 patients diagnosed with PCa were included in this study. All patients had a Gleason score of 6 (GS6) in biopsy, had clinical T2a before surgery and were treated with RP.

Early Plasma Circulating Tumor DNA as a Potential Biomarker of Disease Recurrence in Non-metastatic Prostate Cancer.

Purpose: In non-metastatic prostate cancer (nmPCa) setting, it is important to early identify the patients at risk of biochemical recurrence (BCR) for immediate postoperative intervention. Our study aimed to evaluate the potential clinical utility of circulating tumor DNA (ctDNA) for predicting disease recurrence.

Materials And Methods: This real-world observational study evaluated 161 cases of nmPCa undergoing next-generation sequencing at our institution.

Numb/Parkin-directed mitochondrial fitness governs cancer cell fate via metabolic regulation of histone lactylation.

Cell plasticity and neuroendocrine differentiation in prostate and lung adenocarcinomas are one of the major reasons for therapeutic resistance to targeted therapy. Whether and how metabolic changes contribute to this adenocarcinoma-to-neuroendocrine cell fate transition remains largely unclear. Here we show that neuroendocrine prostate or lung cancer cells possess mostly fragmented mitochondria with low membrane potential and rely on glycolysis for energy metabolism.

TRIM59 is suppressed by androgen receptor and acts to promote lineage plasticity and treatment-induced neuroendocrine differentiation in prostate cancer.

The incidence of treatment-induced neuroendocrine prostate cancer (t-NEPC) has been greatly increasing after the usage of secondgeneration androgen receptor (AR) pathway inhibitors (ARPIs). Neuroendocrine differentiation (NED) is closely associated with ARPI treatment failure and poor prognosis in prostate cancer (PCa) patients. However, the molecular mechanisms of NED are not fully understood.

PD-1 inhibitor plus anlotinib for metastatic castration-resistant prostate cancer: a real-world study.

Management and treatment of terminal metastatic castration-resistant prostate cancer (mCRPC) remains heavily debated. We sought to investigate the efficacy of programmed cell death 1 (PD-1) inhibitor plus anlotinib as a potential solution for terminal mCRPC and further evaluate the association of genomic characteristics with efficacy outcomes. We conducted a retrospective real-world study of 25 mCRPC patients who received PD-1 inhibitor plus anlotinib after the progression to standard treatments.

Efficacy of neoadjuvant docetaxel + cisplatin chemo-hormonal therapy versus docetaxel chemo-hormonal therapy in patients with locally advanced prostate cancer with germline DNA damage repair gene alterations.

Purpose: To assess the efficacy and safety of neoadjuvant docetaxel + cisplatin chemotherapy with androgen deprivation therapy for the treatment of locally advanced prostate cancer (PCa) in patients harboring germline DNA damage repair genes (gDDR) defects.

Methods: We conducted a prospective observational study in patients with locally advanced PCa confirmed with gDDR defects through next-generation sequencing. All patients received either docetaxel + cisplatin (platinum-group) or docetaxel chemo-hormonal therapy (docetaxel group) followed by radical prostatectomy with extended lymphadenectomy.

Gremlin1 is a therapeutically targetable FGFR1 ligand that regulates lineage plasticity and castration resistance in prostate cancer.

Among the greatest hurdles in clinical management of prostate cancer (PCa) are the progression to lethal castration-resistant prostate cancer (CRPC) and the lack of suitable targeted therapies for advanced disease. Here we identify Gremlin1 as a ligand for fibroblast growth factor receptor 1 (FGFR1), which promotes lineage plasticity and drives castration resistance. Importantly, we generate a specific anti-Gremlin1 therapeutic antibody and demonstrate synergistic effect with androgen deprivation therapy (ADT) in CRPC.

Olaparib for Chinese metastatic castration-resistant prostate cancer: A real-world study of efficacy and gene predictive analysis.

To evaluate the real-world effectiveness and gene predictive analysis of olaparib in Chinese patients with metastatic castration-resistant prostate cancer (mCRPC), a multicenter, retrospective, real-world study was conducted by involving Chinese patients with mCRPC from December 2017 to June 2021. Homologous Recombination repair (HRR)gene mutation (HRRm) status was identified using targeted next-generation sequencing (NGS). The primary end point includes prostate-specific antigen (PSA) response rate (PSA).

Use of Circulating Tumor DNA for the Clinical Management of Metastatic Castration-Resistant Prostate Cancer: A Multicenter, Real-World Study.

Background: This study aimed to describe the aberrations of DNA damage repair genes and other important driving genes in Chinese patients with metastatic castration-resistant prostate cancer (mCRPC) using circulating tumor (ctDNA) sequencing and to evaluate the associations between the clinical outcomes of multiple therapies and key genomic alterations in mCRPC, especially DNA damage repair genes.

Patients And Methods: A total of 292 Chinese patients with mCRPC enrolled from 8 centers. Multigene targeted sequencing was performed on 306 ctDNA samples and 23 matched tumor biopsies.

Distinct Response to Platinum-Based Chemotherapy among Patients with Metastatic Castration-Resistant Prostate Cancer Harboring Alterations in Genes Involved in Homologous Recombination.

Purpose: We aimed to explore the association between genomic status and clinical outcome of platinum-based chemotherapy among patients with metastatic castration-resistant prostate cancer (mCRPC).

Materials And Methods: We conducted a retrospective study of 55 patients with mCRPC who received platinum-based chemotherapy after the progression to docetaxel chemotherapy and underwent genomic profiling of 14 homologous recombination (HR) pathway genes. Progression-free survival (PFS) was analyzed using the Kaplan-Meier method.

Efficacy of Neoadjuvant Chemohormonal Therapy in Oligometastatic Hormone-Sensitive Prostate Cancer: A Prospective, Three-Arm, Comparative Propensity Score Match Analysis.

Background: The study aimed to investigate the efficacy and safety outcomes in hormone-sensitive oligometastatic prostate cancer (OMPC) patients treated with docetaxel-based neoadjuvant chemohormonal therapy (NCHT) prior to radical prostatectomy (RP) compared with direct RP and standard androgen deprivation therapy (ADT) alone using propensity score match (PSM) analysis.

Patients And Methods: A single-center, prospective, three-arm study was conducted with hormone-sensitive OMPC patients. Eligible patients (N = 130) were divided into three groups-NCHT, RP, and standard treatment (ST)-and received their respective treatments.

The prognostic nomogram including MRI for locally advanced prostate cancer treated by radical prostatectomy.

Objective: To establish the prognostic nomogram for locally advanced prostate cancer (LAPC) patients treated by radical prostatectomy (RP) based on clinical and multiparametric-MRI (mp-MRI) metrics.

Methods: One hundred and twenty-one patients diagnosed with LAPC were included in this study. They were all examined by mp-MRI within one week before surgery and treated by RP (36 with RP alone, 48 with neoadjuvant hormonal therapy (NHT) and 37 with neoadjuvant chemohormonal therapy (NCHT)).

Targeted Next-Generation Sequencing Reveals Heterogenous Genomic Features in Viscerally Metastatic Prostate Cancer.

Purpose: We sought to explore the genomic features of bone-only metastasis, hepatic metastasis and pulmonary metastasis without liver involvement in prostate cancer using targeted next-generation sequencing.

Materials And Methods: A hybridization capture-based next-generation sequencing was performed to detected genomic alterations in 50 genes, including androgen receptor, DNA damage response and other clinical relevant drivers.

Results: We successfully sequenced circulating tumor DNA from 109 blood samples and 29 metastatic tissue samples from 129 patients with metastatic castration-resistant prostate cancer (metastatic castration-resistant prostate cancer).

HOXD13 suppresses prostate cancer metastasis and BMP4-induced epithelial-mesenchymal transition by inhibiting SMAD1.

The HOX genes are a group of highly conserved Homeobox-containing genes that control the body plan organization during development. However, their contributions to tumorigenesis and tumor progression remain uncertain and controversial. Here we provided evidence of tumor-suppressive activity of HOXD13 in prostate cancer.

Single-cell analysis supports a luminal-neuroendocrine transdifferentiation in human prostate cancer.

Neuroendocrine prostate cancer is one of the most aggressive subtypes of prostate tumor. Although much progress has been made in understanding the development of neuroendocrine prostate cancer, the cellular architecture associated with neuroendocrine differentiation in human prostate cancer remain incompletely understood. Here, we use single-cell RNA sequencing to profile the transcriptomes of 21,292 cells from needle biopsies of 6 castration-resistant prostate cancers.

Comparative Analysis of Genomic Alterations across Castration Sensitive and Castration Resistant Prostate Cancer via Circulating Tumor DNA Sequencing.

Purpose: To explore the genomic profiles of Chinese patients with castration sensitive prostate cancer and those with metastatic castration resistant prostate cancer via germline and circulating tumor DNA sequencing.

Materials And Methods: A hybridization capture based next-generation sequencing assay was used to identify germline and somatic alterations in 50 genes including androgen receptor pathway genes, DNA damage repair pathway genes, and .

Results: We successfully sequenced DNA from 396 blood samples and 32 matched tumor tissue samples from 396 patients.

Surface-enhanced Raman spectroscopy of preoperative serum samples predicts Gleason grade group upgrade in biopsy Gleason grade group 1 prostate cancer.

Purpose: To predict Gleason grade group (GG) upgrade in biopsy Gleason grade group 1 (GG1) prostate cancer (CaP) patients using surface-enhanced Raman spectroscopy (SERS).

Materials And Methods: Preoperative serum samples of patients with biopsy GG1 and subsequent radical prostatectomy were analyzed using SERS. The role of clinical variables and distinctive SERS spectra in the prediction of GG upgrade were evaluated.

Identification of a Zeb1 expressing basal stem cell subpopulation in the prostate.

The basal cell compartment in many epithelial tissues is generally believed to serve as an important pool of stem cells. However, basal cells are heterogenous and the stem cell subpopulation within basal cells is not well elucidated. Here we uncover that the core epithelial-to-mesenchymal transition (EMT) inducer Zeb1 is expressed in a prostate basal cell subpopulation.

The Microbiome of Prostate Fluid Is Associated With Prostate Cancer.

Objectives: To explore the microbiome of the prostatic fluid in high prostate-specific antigen (PSA) patients.

Patients And Methods: The microbiome profiles of prostatic fluid samples from 32 prostate cancer (PCa) patients and 27 non-PCa people were assessed. Microbiome analysis was assessed by massive 16S ribosomal RNA gene sequencing.

Neuroendocrine differentiation markers guide treatment sequence selection in metastatic castration-resistant prostate cancer.

Background: To evaluate the value of the serum neuroendocrine differentiation (NED) markers in helping to select the best treatment sequence of abiraterone acetate (AA) and docetaxel-prednisone (DP) in mCRPC.

Methods: Eighty-eight mCRPC patients were identified (42 in the DP-to-AA group and 46 in the AA-to-DP group). The serum levels of NED markers were measured before the first-line treatment in 88 patients and also before and after DP therapy in 38 patients.

Abiraterone acetate for chemotherapy-naive metastatic castration-resistant prostate cancer: a single-centre prospective study of efficacy, safety, and prognostic factors.

Background: To evaluate the efficacy and safety of abiraterone acetate (AA) plus prednisone compared with prednisone alone in Asian patients with chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC), and to identify predictive factors.

Methods: We reviewed the medical records of 60 patients with chemotherapy-naive mCRPC at Renji Hospital who were treated with AA plus prednisone (n = 43) or prednisone alone (n = 17). All patients were assessed for prostate-specific antigen (PSA) response, PSA progression-free survival (PSA PFS), radiographic progression-free survival (rPFS), and overall survival (OS).