Prostate Cancer

Discovery of CBPD-409 as a Highly Potent, Selective, and Orally Efficacious CBP/p300 PROTAC Degrader for the Treatment of Advanced Prostate Cancer.

CBP/p300 are critical transcriptional coactivators of the androgen receptor (AR) and are promising cancer therapeutic targets. Herein, we report the discovery of highly potent, selective, and orally bioavailable CBP/p300 degraders using the PROTAC technology with CBPD-409 being the most promising compound.

A practical guide for assessing and managing cardiovascular risk during androgen-deprivation therapy in patients with prostate cancer.

Prostate cancer is the most common malignancy among men worldwide, and androgen-deprivation therapy (ADT) is a mainstay of treatment. There are observational data demonstrating an increased risk of cardiovascular events in patients who receive ADT, particularly those who have an elevated baseline cardiovascular risk.

Interaction of patient age and high-grade prostate cancer on targeted biopsies of MRI suspicious lesions.

To evaluate the interaction of patient age and Prostate Imaging-Reporting and Data System (PI-RADS) score in determining the grade of prostate cancer (PCa) identified on magnetic resonance imaging (MRI)-targeted biopsy in older men.

Patterns of B-cell lymphocyte expression changes in pre- and post-malignant prostate tissue are associated with prostate cancer progression.

Inflammation characterized by the presence of T and B cells is often observed in prostate cancer, but it is unclear how T- and B-cell levels change during carcinogenesis and whether such changes influence disease progression.

Real-world prostate-specific antigen reduction and survival outcomes of metastatic hormone-sensitive prostate cancer patients treated with apalutamide: An observational, retrospective, and multicentre study.

Metastatic hormone-sensitive prostate cancer (mHSPC) treatment has changed drastically during the last years with the emergence of androgen receptor-targeted agents (ARTAs). ARTA combined with androgen deprivation therapy has demonstrated better oncological and survival outcomes in these patients.

Clinically-observed FOXA1 mutations upregulate SEMA3C through transcriptional derepression in prostate cancer.

FOXA1 is a pioneer transcription factor that is frequently mutated in prostate, breast, bladder, and salivary gland malignancies. Indeed, metastatic castration-resistant prostate cancer (mCRPC) commonly harbour FOXA1 mutations with a prevalence of 35%.

Case report: Exceptional and durable response to Radium-223 and suspension of androgen deprivation therapy in a metastatic castration-resistant prostate cancer patient.

Despite the development of new therapies in the last few years, metastatic prostate cancer (PCa) is still a lethal disease. Radium-223 (Ra-223) is approved for patients with advanced castration-resistant prostate cancer (CRPC) with bone metastases and no visceral disease.

A Signal-finding Study of Abemaciclib in Heavily Pretreated Patients with Metastatic Castration-Resistant Prostate Cancer: Results from CYCLONE 1.

Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors radically changed the treatment paradigm for breast cancer. Similar to estrogen receptor in breast cancer, androgen receptor signaling activates cyclin D-CDK4/6, driving proliferation and resistance to hormonal manipulation in prostate cancer.

Real-World Evaluation of Primary Versus Secondary Prevention of Skeletal-Related Events in Metastatic Castration-Resistant Prostate Cancer.

Anti-osteoclast treatment with denosumab or zoledronate is known to effectively reduce the need for radiotherapy to bone and other skeletal-related events (SREs) in patients with metastatic castration-resistant prostate cancer (mCRPC).

Can we predict pathology without surgery? Weighing the added value of multiparametric MRI and whole prostate radiomics in integrative machine learning models.

To test the ability of high-performance machine learning (ML) models employing clinical, radiological, and radiomic variables to improve non-invasive prediction of the pathological status of prostate cancer (PCa) in a large, single-institution cohort.

Critical Evaluation of Artificial Intelligence as a Digital Twin of Pathologists for Prostate Cancer Pathology - Beyond the Abstract

Prostate cancer pathology constitutes a cornerstone in clinical management, albeit its inherent time-consuming nature. Artificial intelligence (AI) offers a promising avenue for expediting prostate cancer detection and grading histological patterns.

MRI in-bore biopsy following MRI/US fusion-guided biopsy in patients with persistent suspicion of clinically significant prostate cancer.

Patients with suspicion of clinically significant prostate cancer (csPC) on multiparametric prostate MRI (mpMRI) but negative or inconclusive MRI/US fusion-guided biopsy (FB) can be challenging in clinical practice.

Variation in Access to Palliative Radiotherapy in Prostate Cancer: A Population-Based Study in Canada.

As a result of improvements in cancer therapies, patients with metastatic malignancies are living longer, and the role of palliative radiotherapy has become increasingly recognized. However, access to adequate palliative radiotherapy may continue to be a challenge, as is evident from the high proportion of patients dying of prostate cancer who never receive palliative radiotherapy.

A global phase II randomized trial comparing oral taxane ModraDoc006/r to intravenous docetaxel in metastatic castration resistant prostate cancer.

ModraDoc006, an oral formulation of docetaxel, is co-administered with the cytochrome P450-3A4 and P-glycoprotein inhibitor, ritonavir (r): ModraDoc006/r. The preliminary efficacy and safety of oral ModraDoc006/r was evaluated in a global randomized phase II trial and compared to the current standard chemotherapy regimen of intravenous (i.

Three- and Seven-month Prostate-specific Antigen Levels as Prognostic Markers for Overall Survival in Metastatic Hormone-sensitive Prostate Cancer: Results from SWOG S1216, a Phase 3 Randomized Trial of Androgen Deprivation Plus Orteronel or Bicalutamide.

A robust decrease in prostate-specific antigen (PSA) in response to androgen deprivation therapy (ADT) has been evaluated as a prognostic factor in patients with metastatic hormone-sensitive prostate cancer (mHSPC) since 2006, but the treatment of mHSPC has since evolved to include intensified therapy.

Tissue-Based Genomic Testing in Prostate Cancer: 10-Year Analysis of National Trends on the Use of Prolaris, Decipher, ProMark, and Oncotype DX.

Prostate cancer (PCa) management is moving towards patient-tailored strategies. Advances in molecular and genetic profiling of tumor tissues, integrated with clinical risk assessments, provide deeper insights into disease aggressiveness.

RAPHIA: A deep learning pipeline for the registration of MRI and whole-mount histopathology images of the prostate.

Image registration can map the ground truth extent of prostate cancer from histopathology images onto MRI, facilitating the development of machine learning methods for early prostate cancer detection.

Ectopic JAK-STAT activation enables the transition to a stem-like and multilineage state conferring AR-targeted therapy resistance.

Emerging evidence indicates that various cancers can gain resistance to targeted therapies by acquiring lineage plasticity. Although various genomic and transcriptomic aberrations correlate with lineage plasticity, the molecular mechanisms enabling the acquisition of lineage plasticity have not been fully elucidated.

Loss of CHD1 Promotes Heterogeneous Mechanisms of Resistance to AR-Targeted Therapy via Chromatin Dysregulation.

Metastatic prostate cancer is characterized by recurrent genomic copy number alterations that are presumed to contribute to resistance to hormone therapy. We identified CHD1 loss as a cause of antiandrogen resistance in an in vivo small hairpin RNA (shRNA) screen of 730 genes deleted in prostate cancer.

Gender-Based Disparity Exists in the Surgical Experience of Female and Male Urology Residents

Objective
To determine if a discrepancy exists in the number and type of cases logged between female and male urology residents.

Materials and Methods
ACGME case log data from 13 urology residency programs was collected from 2007 to 2020. The number and type of cases for each resident were recorded and correlated with resident gender and year of graduation. The median, 25th, and 75th percentiles number of cases were calculated by gender and then compared between female and male residents using Wilcoxon rank sum test.

Results
A total of 473 residents were included in the study, 100 (21%) were female. Female residents completed significantly fewer cases, 2174, compared to male residents, 2273 (P = .038). Analysis by case type revealed male residents completed significantly more general urology (526 vs 571, P = .011) and oncology cases (261 vs 280, P = .026). Additionally, female residents had a 1.3-fold increased odds of logging a case in the assistant role than male residents (95% confidence interval: 1.27-1.34, P < .001).

Conclusion
Gender-based disparity exists within the urology training of female and male residents. Male residents logged nearly 100 more cases than female residents over 4 years, with significant differences in certain case subtypes and resident roles. The ACGME works to provide an equal training environment for all residents. Addressing this finding within individual training programs is critical.

Kathryn A Marchetti,1 Charles A Ferreri,2 Emma C Bethel,3 Bori Lesser-Lee,4 Stephanie Daignault-Newton,5 Suzanne Merrill,6 Gina M Badalato,7 Elizabeth T Brown,8 Thomas Guzzo,9 R Houston Thompson,10 Adam Klausner,11 Richard Lee,12 Dipen J Parekh,13 Jay D Raman,14 Adam Reese,15 Patrick Shenot,16 Daniel H Williams,17 Stanley Zaslau,18 Kate H Kraft5

  1. University of Pittsburgh Medical Center, Department of Urology, Pittsburgh, PA.
  2. Vanderbilt University Medical Center, Department of Urology, Nashville, TN.
  3. University of North Carolina School of Medicine, Department of Urology, Chapel Hill, NC.
  4. University of Michigan Medical School, Ann Arbor, MI.
  5. University of Michigan Health System, Department of Urology, Ann Arbor, MI.
  6. United Urology Group, Aurora, CO.
  7. Columbia University, Department of Urology, New York, NY.
  8. MedStar Georgetown University Hospital, Department of Urology, Washington, DC.
  9. University of Pennsylvania, Department of Urology, Philadelphia, PA.
  10. Mayo Clinic Rochester, Department of Urology, Rochester, MN.
  11. Virginia Commonwealth University, Division of Urology, Richmond, VA.
  12. Weill Cornell Medicine, Department of Urology, New York, NY.
  13. University of Miami Health System, Department of Urology, Miami, FL.
  14. Pennsylvania State University College of Medicine, Department of Urology, Hershey, PA.
  15. Temple University, Department of Urology, Philadelphia, PA.
  16. Jefferson Health, Department of Urology, Philadelphia, PA.
  17. University of Wisconsin, Department of Urology, Madison, WI.
  18. West Virginia University School of Medicine Urology, Morgantown, WV.
Source: Gender-Based Disparity Exists in the Surgical Experience of Female and Male Urology Residents