Bilateral acute macular neuroretinopathy following influenza A infection.

A previously healthy 18-year-old female presented with bilateral cecocentral scotomas two-days after onset of confirmed Influenza A infection, consistent with a post-viral acute macular neuroretinopathy (AMN). Fundoscopy revealed bilateral small petaloid lightening in the nasal macula, and optical coherence tomography revealed thinning of the interdigitation zone, ellipsoid zone, and outer nuclear layer bilaterally. Scotomas and associated imaging findings showed partial improvement in the weeks following diagnosis.

Expression Patterns of DLL3 across Neuroendocrine and Non-neuroendocrine Neoplasms Reveal Broad Opportunities for Therapeutic Targeting.

DLL3-targeted therapies have recently shown robust clinical efficacy in aggressive neuroendocrine cancers, positioning them to fulfill a great unmet need in these settings. Here, we examine the clinical and biological correlates of DLL3 expression in both neuroendocrine and non-neuroendocrine cancers. Our findings may stimulate the development and application of DLL3-targeted therapies, as well as other precision therapies, in neuroendocrine cancers and beyond.

AR alterations inform circulating tumor DNA detection in metastatic castration resistant prostate cancer patients.

Circulating tumor DNA (ctDNA) in plasma cell free DNA (cfDNA) of cancer patients is associated with poor prognosis, but is challenging to detect from low plasma volumes. In metastatic castration-resistant prostate cancer (mCRPC), ctDNA assays are needed to prognosticate outcomes of patients treated with androgen receptor (AR) inhibitors. We develop a custom targeted cfDNA sequencing assay, named AR-ctDETECT, to detect ctDNA in limiting plasma cfDNA available from mCRPC patients in the Alliance A031201 randomized phase 3 trial of enzalutamide with or without abiraterone.

Implementing evidence-based strategies for men with biochemically recurrent and advanced prostate cancer: Consensus recommendations from the US Prostate Cancer Conference 2024.

Current US clinical practice guidelines for advanced prostate cancer management contain recommendations based on high-level evidence from randomized controlled trials; however, these guidelines do not address the nuanced clinical questions that are unanswered by prospective trials but nonetheless encountered in day-to-day practice. To address these practical questions, the 2024 US Prostate Cancer Conference (USPCC 2024) was created to generate US-focused expert clinical decision-making guidance for circumstances in which level 1 evidence is lacking. At the second annual USPCC meeting (USPCC 2024), a multidisciplinary panel of experts convened to discuss ongoing clinical challenges related to 5 topic areas: biochemical recurrence; metastatic, castration-sensitive prostate cancer; poly [ADP-ribose] polymerase inhibitors; prostate-specific membrane antigen radioligand therapy; and metastatic, castration-resistant prostate cancer.

A novel interaction between RNA mA methyltransferase METTL3 and RREB1.

Regulation of gene expression is achieved through the modulation of regulatory inputs both pre- and post-transcriptionally. Methyltransferase-like 3 (METTL3) is a key player in pre-mRNA processing, actively catalyzing N6-methyladenosine (m6A). Among the most enriched mRNA targets of METTL3 is the Ras Responsive Element Binding Protein 1 (RREB1), a transcription factor which functions to govern cell fate, proliferation and DNA repair.

Androgen production, uptake, and conversion (APUC) genes define prostate cancer patients with distinct clinical outcomes.

BACKGROUNDProstate cancer (PC) is driven by aberrant signaling of the androgen receptor (AR) or its ligands, and androgen deprivation therapies (ADTs) are a cornerstone of treatment. ADT responsiveness may be associated with germline changes in genes that regulate androgen production, uptake, and conversion (APUC).METHODSWe analyzed whole-exome sequencing (WES) and whole-transcriptome sequencing (WTS) data from prostate tissues (SU2C/PCF, TCGA, GETx).

Synchronous primary endometrial adenocarcinoma and primary squamous cell carcinoma of the cervix: A case report and literature review.

The synchronous occurrence of primary endometrioid endometrial adenocarcinoma and primary squamous cell carcinoma of the cervix is exceedingly rare. Ovarian and endometrial cancers represent the most frequently observed forms of synchronous gynaecological malignancies. In contrast, in less than 1 % of cases, endometrial cancer coexists with primary cervical cancer.

PRESTO: A Phase III, Open-Label Study of Intensification of Androgen Blockade in Patients With High-Risk Biochemically Relapsed Castration-Sensitive Prostate Cancer (AFT-19).

Purpose: Patients with biochemically recurrent prostate cancer (BRPC) after radical prostatectomy and a short PSA doubling time are at risk for distant metastases. Apalutamide, an androgen receptor antagonist, and abiraterone acetate plus prednisone (AAP) prolong survival in the metastatic setting. We evaluated whether intensification of androgen-deprivation therapy (ADT) improves outcomes in BRPC.

Molecular Characterization of TFE3-Rearranged Renal Cell Carcinoma: A Comparative Study With Papillary and Clear Cell Renal Cell Carcinomas.

TFE3-rearranged renal cell carcinoma (rRCC) is a rare subtype of renal cell carcinomas belonging to the MiT family translocation RCC. To further elucidate the co-alterations that occur along with TFE3 fusions in rRCC, we characterized the genomic, transcriptional, and immune landscapes in comparison to clear cell (ccRCC) and papillary renal cell carcinoma (pRCC). Next-generation sequencing of RNA (whole transcriptome) and DNA (592-gene panel or whole exome) for rRCC (N = 20), pRCC (N = 20), and ccRCC samples (N = 392) was performed.

Comprehensive genomic profiling of penile squamous cell carcinoma and the impact of human papillomavirus status on immune-checkpoint inhibitor-related biomarkers.

Background: Advanced penile squamous cell carcinoma (pSCC) is a rare and aggressive malignancy with limited success of immune-checkpoint inhibitors (ICIs). Approximately half of pSCC cases are associated with human papillomavirus (HPV) infection.

Methods: Evaluation was done retrospectively of the landscape of somatic alterations and ICI-related biomarkers in pSCC by using the Caris Life Sciences data set with the aim to establish signatures for HPV-dependent oncogenesis.

Clinical outcomes in patients with metastatic castrate-resistant prostate cancer treated with abiraterone with or without ongoing androgen deprivation therapy: A retrospective case-control study.

Introduction: Abiraterone and concurrent androgen deprivation therapy (ADT) are used in the treatment of patients with metastatic castration-resistant prostate cancer. Recently, it has been suggested that the use of abiraterone alone (without ADT) may have comparable efficacy to abiraterone with ongoing ADT. Here, we sought to assess the impact of ADT cessation in patients beginning abiraterone for castration-resistant prostate cancer.

Rucaparib for the Treatment of Metastatic Castration-resistant Prostate Cancer Associated with a DNA Damage Repair Gene Alteration: Final Results from the Phase 2 TRITON2 Study.

Background: Initial TRITON2 (NCT02952534) results demonstrated the efficacy of rucaparib 600 mg BID in patients with metastatic castration-resistant prostate cancer (mCRPC) associated with a BRCA1 or BRCA2 (BRCA) or other DNA damage repair (DDR) gene alteration.

Objective: To present the final data from TRITON2.

Design, Setting, And Participants: TRITON2 enrolled patients with mCRPC who had progressed on one or two lines of next-generation androgen receptor-directed therapy and one taxane-based chemotherapy.

Metastatic Prostate Cancers with BRCA2 versus ATM Mutations Exhibit Divergent Molecular Features and Clinical Outcomes.

Purpose: In patients with metastatic prostate cancer (mPC), ATM and BRCA2 mutations dictate differences in PARPi inhibitor response and other therapies. We interrogated the molecular features of ATM- and BRCA2-mutated mPC to explain the divergent clinical outcomes and inform future treatment decisions.

Experimental Design: We examined a novel set of 1,187 mPCs after excluding microsatellite-instable (MSI) tumors.

H2A monoubiquitination: insights from human genetics and animal models.

Metazoan development arises from spatiotemporal control of gene expression, which depends on epigenetic regulators like the polycomb group proteins (PcG) that govern the chromatin landscape. PcG proteins facilitate the addition and removal of histone 2A monoubiquitination at lysine 119 (H2AK119ub1), which regulates gene expression, cell fate decisions, cell cycle progression, and DNA damage repair. Regulation of these processes by PcG proteins is necessary for proper development, as pathogenic variants in these genes are increasingly recognized to underly developmental disorders.

ALAN is a computational approach that interprets genomic findings in the context of tumor ecosystems.

Gene behavior is governed by activity of other genes in an ecosystem as well as context-specific cues including cell type, microenvironment, and prior exposure to therapy. Here, we developed the Algorithm for Linking Activity Networks (ALAN) to compare gene behavior purely based on patient -omic data. The types of gene behaviors identifiable by ALAN include co-regulators of a signaling pathway, protein-protein interactions, or any set of genes that function similarly.

External Validation of a Prognostic Model of Overall Survival in Men With Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer.

Purpose: We have previously developed and externally validated a prognostic model of overall survival (OS) in men with metastatic, castration-resistant prostate cancer (mCRPC) treated with docetaxel. We sought to externally validate this model in a broader group of men with docetaxel-naïve mCRPC and in specific subgroups (White, Black, Asian patients, different age groups, and specific treatments) and to classify patients into validated two and three prognostic risk groupings on the basis of the model.

Methods: Data from 8,083 docetaxel-naïve mCRPC men randomly assigned on seven phase III trials were used to validate the prognostic model of OS.

Management of patients with advanced prostate cancer-metastatic and/or castration-resistant prostate cancer: Report of the Advanced Prostate Cancer Consensus Conference (APCCC) 2022.

Background: Innovations in imaging and molecular characterisation together with novel treatment options have improved outcomes in advanced prostate cancer. However, we still lack high-level evidence in many areas relevant to making management decisions in daily clinical practise. The 2022 Advanced Prostate Cancer Consensus Conference (APCCC 2022) addressed some questions in these areas to supplement guidelines that mostly are based on level 1 evidence.

Quality of life outcomes for patients with metastatic castration-resistant prostate cancer and pretreatment prognostic score.

Background: A prognostic risk score (Halabi score) in metastatic castration-resistant prostate cancer (mCRPC) accurately predicts overall survival, but its association with quality of life (QOL) has not been defined. We hypothesize that a higher pretreatment Halabi score is associated with worse QOL outcomes over time in mCRPC patients.

Methods: Patient-level data from the docetaxel plus prednisone control arm of Mainsail, a Phase 3 clinical trial in mCRPC were accessed via ProjectDataSphere.

Rucaparib or Physician's Choice in Metastatic Prostate Cancer.

Background: In a phase 2 study, rucaparib, an inhibitor of poly(ADP-ribose) polymerase (PARP), showed a high level of activity in patients who had metastatic, castration-resistant prostate cancer associated with a deleterious alteration. Data are needed to confirm and expand on the findings of the phase 2 study.

Methods: In this randomized, controlled, phase 3 trial, we enrolled patients who had metastatic, castration-resistant prostate cancer with a , , or alteration and who had disease progression after treatment with a second-generation androgen-receptor pathway inhibitor (ARPI).