Personalized Medicine: Leave no Patient Behind; Report From the 2024 Coffey-Holden Prostate Cancer Academy Meeting.

Introduction: The 11th Annual 2024 Coffey - Holden Prostate Cancer Academy (CHPCA) Meeting, was themed "Personalized Medicine: Leave No Patient Behind," and was held from June 20 to 23, 2024 at the University of California, Los Angeles, Luskin Conference Center, in Los Angeles, CA.

Methods: The CHPCA Meeting is an academy-styled annual conference organized by the Prostate Cancer Foundation, to focus discussion on the most critical emerging research that have the greatest potential to advance knowledge of prostate cancer biology and treatment. The 2024 CHPCA Meeting was attended by 75 academic investigators and included 37 talks across 8 sessions.

Role of Chemokines and Cytokines in Prostate Cancer Skeletal Metastasis.

Purpose Of Review: Once prostate cancer (PCa) bone metastases develop, the prognosis dramatically declines. The precise mechanisms regulating bone metastasis remain elusive. This review will explore recent findings related to cytokines and chemokines in the process of bone metastases.

Bystanders or active players: the role of extra centrosomes as signaling hubs.

Centrosomes serve as microtubule-organizing organelles that function in spindle pole organization, cell cycle progression, and cilia formation. A non-canonical role of centrosomes that has gained traction in recent years is the ability to act as signal transduction centers. Centrosome amplification, which includes numerical and structural aberrations of centrosomes, is a candidate hallmark of cancer.

Single-Cell Proteomic and Transcriptomic Characterization of Drug-Resistant Prostate Cancer Cells Reveals Molecular Signatures Associated with Morphological Changes.

This study delves into the proteomic intricacies of drug-resistant cells (DRCs) within prostate cancer, which are known for their pivotal roles in therapeutic resistance, relapse, and metastasis. Utilizing single-cell proteomics (SCP) with an optimized high-throughput Data Independent Acquisition (DIA) approach with the throughput of 60 sample per day, we characterized the proteomic landscape of DRCs in comparison to parental PC3 cells. This optimized DIA method allowed for robust and reproducible protein quantification at the single-cell level, enabling the identification and quantification of over 1,300 proteins per cell on average.

Polyploid cancer cells reveal signatures of chemotherapy resistance.

Therapeutic resistance in cancer significantly contributes to mortality, with many patients eventually experiencing recurrence after initial treatment responses. Recent studies have identified therapy-resistant large polyploid cancer cells in patient tissues, particularly in late-stage prostate cancer, linking them to advanced disease and relapse. Here, we analyzed bone marrow aspirates from 44 advanced prostate cancer patients and found the presence of CTC-IGC was significantly associated with poorer progression-free survival.

Identification of a 5-gene signature panel for the prediction of prostate cancer progression.

Background: Despite nearly 100% 5-year survival for localised prostate cancer, the survival rate for metastatic prostate cancer significantly declines to 32%. Thus, it is crucial to identify molecular indicators that reflect the progression from localised disease to metastatic prostate cancer.

Methods: To search for molecular indicators associated with prostate cancer metastasis, we performed proteomic analysis of rapid autopsy tissue samples from metastatic prostate cancer (N = 8) and localised prostate cancer (N = 2).

Alterations of the chemical profile of cholesterol in cancer tissue as traced with ToF-SIMS.

Cancer has become one of the leading causes of death, with approximately ten million people worldwide dying from cancer each year. In most cases, cancer spreads to remote organs and develops a resistance to therapy. To reduce the deadly impact of cancer, novel targets for markers for early detection are necessary.

Initial Experience with [Lu]Lu-PSMA-617 After Regulatory Approval for Metastatic Castration-Resistant Prostate Cancer: Efficacy, Safety, and Outcome Prediction.

[Lu]Lu-PSMA-617 was approved by the U.S. Food and Drug Administration for patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC).

Polyploid cancer cells reveal signatures of chemotherapy resistance.

Therapeutic resistance in cancer significantly contributes to mortality, with many patients eventually experiencing recurrence after initial treatment responses. Recent studies have identified therapy-resistant large polyploid cancer cells in patient tissues, particularly in late-stage prostate cancer, linking them to advanced disease and relapse. Here, we analyzed bone marrow aspirates from 44 advanced prostate cancer patients and found the presence of circulating tumor cells with increased genomic content (CTC-IGC) was significantly associated with poorer progression-free survival.

Oncogenic signaling in the adult prostate-like accessory gland leads to activation of a conserved pro-tumorigenic program, in the absence of proliferation.

models for tumorigenesis and metastasis have revealed conserved mechanisms of signaling that are also involved in mammalian cancer. Many of these models use the proliferating tissues of the larval stages of development, when tissues are highly mitotically active, or stem cells are abundant. Fewer tumorigenesis models use adult animals to initiate tumor formation when many tissues are largely terminally differentiated and postmitotic.

Urinary extracellular vesicle-derived miR-126-3p predicts lymph node invasion in patients with high-risk prostate cancer.

To investigate extracellular vesicles (EVs), biomarkers for predicting lymph node invasion (LNI) in patients with high-risk prostate cancer (HRPCa), plasma, and/or urine samples were prospectively collected from 45 patients with prostate cancer (PCa) and five with benign prostatic hyperplasia (BPH). Small RNA sequencing was performed to identify miRNAs in the EVs. All patients with PCa underwent radical prostatectomy and extended pelvic lymph node dissection.

Prostate-Specific Membrane Antigen PET Response Associates with Metastasis-Free Survival After Stereotactic Ablative Radiation in Oligometastatic Prostate Cancer.

Purpose: Emerging data suggest that metastasis-directed therapy (MDT) improves outcomes in patients with oligometastatic castration-sensitive prostate cancer (omCSPC). Prostate-specific membrane antigen positron emission tomography (PSMA-PET) can detect occult metastatic disease, and PSMA response has been proposed as a biomarker for treatment response. Herein, we identify and validate a PSMA-PET biomarker for metastasis-free survival (MFS) following MDT in omCSPC.

Punctuational evolution is pervasive in distal site metastatic colonization.

The evolution of metastasis represents a lethal stage of cancer progression. Yet, the evolutionary kinetics of metastatic disease remain unresolved. Here, using single cell CRISPR-Cas9 lineage tracing data, we show that in metastatic disease, gradual molecular evolution is punctuated by episodes of rapid evolutionary change associated with lineage divergence.

Urinary extracellular vesicle-derived miR-126-3p predicts lymph node invasion in patients with high-risk prostate cancer.

To investigate extracellular vesicles (EVs) biomarkers for predicting lymph node invasion (LNI) in patients with high-risk prostate cancer (HRPCa), plasma and/or urine samples were prospectively collected from 45 patients with prostate cancer (PCa) and five with benign prostatic hyperplasia (BPH). Small RNA sequencing was performed to identify miRNAs in the EVs. All patients with PCa underwent radical prostatectomy and extended pelvic lymph node dissection.

Exploration of drug resistance mechanisms in triple negative breast cancer cells using a microfluidic device and patient tissues.

Chemoresistance is a major cause of treatment failure in many cancers. However, the life cycle of cancer cells as they respond to and survive environmental and therapeutic stress is understudied. In this study, we utilized a microfluidic device to induce the development of doxorubicin-resistant (DOXR) cells from triple negative breast cancer (TNBC) cells within 11 days by generating gradients of DOX and medium.