Castration-resistant Prostate Cancer Research Articles

Metabolic Reprogramming of Cancer‐Associated Fibroblasts: Transforming Tumor Accomplices into Immunotherapeutic Allies

AbstractCancer‐associated fibroblasts (CAFs) play a pivotal role in the metabolic symbiosis that drives tumor proliferation and immune evasion. Paradoxically, eliminating CAFs can disrupt tissue homeostasis and potentially accelerate tumor spread. To address this challenge, this study proposes a novel strategy to reprogram CAFs, transforming them into “anchors” and “fuel stations” for anti‐tumor immune cells, thereby enhancing the immune response against tumors. Utilizing a fibroblast‐specific lipid nanoparticle (LNP) delivery system, key metabolic genes in CAFs are targeted and downregulated, specifically hexokinase 2 (HK2) and mitochondrial cytochrome c oxidase I (MTCO1). The dual inhibition of glycolysis and mitochondrial respiration in CAFs consequently results in glucose overload and mitochondrial dysfunction. As a result, these energy‐deprived CAFs exhibit high expression of MHC II molecules and inflammatory cytokines, promoting immune cell infiltration and providing essential fuel for subsequent activation and proliferation. Furthermore, this metabolic reprogramming results in reduced angiogenesis and an immune microenvironment characterized by M1 macrophage polarization and enhanced lymphocyte infiltration. Consequently, this approach improves the efficacy of immune checkpoint inhibitors (ICIs) in castration‐resistant prostate cancer (CRPC). Thus, the reprogramming of CAFs into immune cell allies offers a promising strategy to overcome the limitations of current ICIs therapies.

The value of real world evidence and pragmatic trials in advanced prostate cancer- insights from the electronic Prostate Cancer Australian and Asian Database

Prostate cancer is a common malignancy with an increasing incidence in ageing populations. However, older patients with prostate cancer are often underrepresented in traditional clinical trials. The electronic Prostate Cancer Australian and Asian Database (ePAD) is a multi-centre, multi-national prospective clinical registry, that records real world data from a broader population. An analysis of the first 753 metastatic castration-resistant prostate cancer (mCRPC) patients within ePAD demonstrated that 43% were aged 75 years and older. Older patients were more likely to have comorbidities including ischemic heart disease, diabetes and previous stroke. Treatment outcomes were similar in all age groups. However, older patients receiving chemotherapy were more likely to stop treatment due to toxicity. Furthermore, in a smaller ePAD analysis involving additional chart reviews within 3 high volume centres, at least one relative or absolute contraindication to abiraterone was seen in 72% of our cohort and with enzalutamide in 14%. In total, 47% had potential clinically significant drug interactions with abiraterone and 67% with enzalutamide. Registry-based randomised controlled trials (RRCTs) are a novel trial methodology aiming to bridge the gap between retrospective registry analyses and traditional randomised controlled trials. We conducted the REAL-Pro study in advanced prostate cancer, comparing cognition, depression and falls risk between CRPC patients receiving abiraterone or enzalutamide. The study closed early due to slow recruitment and a changing treatment landscape, highlighting the need for further research to understand clinician and patient perspectives towards pragmatic trials such as RRCTs and subsequently develop strategies to optimise future trial design and recruitment.

Triplet therapy for metastatic castration-sensitive prostate cancer: Rationale and clinical evidence.

Prostate cancer (PC) growth is hormone-dependent and it frequently develops distant metastases as disease progresses. Patients with metastatic castration-sensitive prostate cancer (mCSPC) initially respond to androgen deprivation therapy (ADT) but eventually become refractory and develop metastatic castration-resistant prostate cancer (mCRPC). Castration-resistance is associated with high lethality and metastases confer poor prognosis, therefore unmet needs in treatment for mCSPC remain high. So far, improvements in survival in mCSPC have been achieved by doublet combination therapy such as docetaxel or an androgen-receptor signaling inhibitor (ARSI) in addition to ADT. Further, recent phase 3 trials have shown that triplet therapy-a combination of ARSI, docetaxel, and ADT improves prognosis compared with docetaxel plus ADT in mCSPC. PC tumors manifest intra- and inter-tumoral heterogeneity at both the genetic and phenotypic level. As heterogeneity increases during sequential treatment and disease progression, it is reasonable to initiate combination therapy using drugs with different mechanisms of action early in the course of disease, such as mCSPC. Previous research about tumor heterogeneity and drug resistant mechanism support this rationale, as well as preclinical studies and real-world data provide the scientific evidence of benefit by combining ARSI and docetaxel. Here, we review the rationale and clinical evidence for triplet therapy in patients with mCSPC.

Talazoparib plus enzalutamide versus olaparib plus abiraterone acetate and niraparib plus abiraterone acetate for metastatic castration-resistant prostate cancer: a matching-adjusted indirect comparison.

Without head-to-head trials between talazoparib+enzalutamide (TALA + ENZA), olaparib+abiraterone acetate (OLAP + AAP), and niraparib plus AAP (NIRA + AAP) the ability to evaluate their relative efficacy as first-line (1 L) treatment in metastatic castration-resistant prostate cancer (mCRPC) is limited. The objective of this study was to assess the relative efficacy between TALA + ENZA (TALAPRO-2) versus OLAP + AAP (PROpel) and NIRA + AAP (MAGNITUDE) in 1 L mCRPC via a matching-adjusted indirect treatment comparison (MAIC). Patient-level data from TALAPRO-2 and published data from PROpel and MAGNITUDE were used. TALAPRO-2 data were reweighted to satisfy the eligibility criteria for PROpel and MAGNITUDE. Talazoparib (0.5 mg/day) plus enzalutamide (160 mg/day) was compared to olaparib (300 mg twice daily) plus abiraterone acetate (1000 mg/day) and niraparib (200 mg/day) plus abiraterone acetate (1000 mg/day). Hazard ratios (HRs) were calculated for radiographic progression-free survival (rPFS) and overall survival (OS), and odds ratios (ORs) for prostate-specific antigen (PSA) response and objective response rate (ORR). Additional efficacy outcomes were assessed. In all-comers, TALA + ENZA was statistically superior to OLAP + AAP for rPFS (HR: 0.727; 95% confidence interval [CI]: 0.565, 0.935) and PSA response (OR: 1.663; 1.101, 2.510), and numerically favored for OS (HR: 0.847; 0.667, 1.076) and ORR (OR: 1.109; 0.646, 1.903). In patients with homologous recombination repair mutations (HRRm), relative to NIRA + AAP, TALA + ENZA was statistically superior for rPFS (HR: 0.460; 0.280, 0.754), and numerically favored for OS (HR: 0.601; 0.347, 1.041) and ORR (OR: 1.524; 0.579, 4.016). Results suggest that TALA + ENZA may provide improvements in clinical outcomes relative to OLAP + AAP and NIRA + AAP in 1 L mCRPC; however, inherent limitations associated with the complexity of the analyses must be considered.

Real-world efficacy and safety of combined first-line treatment with PARP inhibitors and novel hormonal therapy in mCRPC patients with HRR gene mutations

ObjectiveThis study evaluated the real-world efficacy and safety of combining PARP inhibitors with novel hormonal therapy (NHT) as a first-line treatment in Chinese patients with metastatic castration-resistant prostate cancer (mCRPC) harboring homologous recombination repair (HRR) gene mutations.MethodsWe enrolled 41 mCRPC patients who received at least 1 month of combined treatment with PARP inhibitors and NHT. Patients were divided into two groups: Cohort A (mutations in BRCA1, BRCA2, or ATM genes) and Cohort B (mutations in other HRR genes). The primary endpoint was imaging-based progression-free survival (PFS), with secondary endpoints including objective response rate (ORR), disease control rate (DCR), overall survival (OS), PSA50 response, and adverse events (AEs). To ensure accurate research results and control confounding factors, we will employ multivariate Cox proportional hazards models to evaluate key variables affecting mCRPC patient survival outcomes.ResultsThis study enrolled 41 patients, 22 in Cohort A and 19 in Cohort B. The median PFS for all patients was 21.8 months, and the median OS had yet to be reached. The overall ORR was 48.8%, and the DCR was 61.0%. Specifically, the median PFS for Cohort A was 21.8 months compared to 14.5 months for Cohort B. The median OS had yet to be reached for either cohort. Regarding efficacy, 81.8% of patients in Cohort A and 73.7% in Cohort B achieved a PSA50 response. Imaging assessments showed ORRs of 54.6% for Cohort A and 42.1% for Cohort B, with DCRs of 72.7% and 47.4%, respectively. 85.4% of patients experienced grade 1 or 2 adverse events, and 51.2% encountered grade 3 or 4. In the multivariate Cox regression analysis focusing on PFS, the Gleason score was identified as a significant predictor (HR = 5.8, 95% CI: 1.65–20.2, p = 0.006).ConclusionCombined first-line treatment with PARP inhibitors and NHT is effective and well-tolerated in mCRPC patients with HRR gene mutations, particularly those with BRCA1, BRCA2, or ATM mutations. These findings underscore the potential of this therapeutic combination in managing mCRPC in the Chinese population, suggesting a favorable outcome for those with specific genetic backgrounds.

Prognostic value of the HALP score in metastatic castration-resistant prostate cancer: an analysis combined with time to castration resistance

Prognostic value of the HALP score in metastatic castration-resistant prostate cancer: an analysis combined with time to castration resistance

Successful Management of Disseminated Intravascular Coagulation in Metastatic Castrate-Resistant Prostate Cancer With Lutetium-177: A Case Report and Review of the Literature

Successful Management of Disseminated Intravascular Coagulation in Metastatic Castrate-Resistant Prostate Cancer With Lutetium-177: A Case Report and Review of the Literature

Comparative analysis of gut microbiota in hormone-sensitive and castration-resistant prostate cancer in Japanese men.

Gut microbiota plays a crucial role in the development and progression of prostate cancer, with previous studies indicating that certain bacterial taxa are more abundant in castration-resistant prostate cancer (CRPC) compared to hormone-sensitive prostate cancer (HSPC). Notably, the composition of gut microbiota can vary significantly by geographic region, and Japanese individuals have a distinct microbial profile. However, research exploring these differences within Japanese populations remains limited. This study investigated the gut microbiota differences between Japanese men with HSPC and CRPC and further validated these findings using a transgenic mouse model. Rectal swab samples were collected from 140 Japanese men diagnosed with HSPC (n = 84) or CRPC (n = 56) between September 2020 and July 2022. Gut microbiota composition was analyzed using 16S rRNA gene sequencing. Additionally, Pten-KO mice, which model the progression from HSPC to CRPC, underwent similar microbiota analysis. Results revealed significant differences in gut microbiota composition between HSPC and CRPC patients. Specifically, the CRPC group showed a higher abundance of Firmicutes, including Gemella and Lactobacillus, compared to the HSPC group. These differences were mirrored in the mouse model, where CRPC mice also showed an increase in these bacteria. This study identifies distinct microbial differences between HSPC and CRPC in Japanese men, suggesting that Gemella and Lactobacillus may be associated with the progression to castration resistance in prostate cancer. These findings suggest that gut microbiota differences may be associated with prostate cancer progression. Further research is needed to explore the potential of targeting the microbiota as a therapeutic strategy.

Targeting Androgen Receptor Variants in Castration-Resistant Prostate Cancer (CRPC)

Castration-resistant prostate cancer (CRPC) remains a lethal stage of prostate cancer, characterized by resistance to androgen deprivation therapy (ADT) and poor clinical prognosis. One of the key drivers in CRPC progression is the androgen receptor (AR), specifically the emergence of androgen receptor variants (AR-Vs) that sustain AR signaling even in the absence of androgens. AR-Vs, such as AR-V7, promote androgen-independent activation of oncogenic pathways, leading to uncontrolled cell proliferation and therapeutic resistance. Targeting AR-Vs offers a promising therapeutic strategy to manage CRPC effectively. This review explores the molecular mechanisms underpinning AR-V expression, examines the roles of major AR variants in CRPC progression, and evaluates current and emerging therapies targeting AR-Vs. By summarizing recent advancements and the limitations of current approaches, we highlight potential future directions to improve therapeutic outcomes for CRPC patients. Keywords: Androgen receptor variants, Castration-resistant prostate cancer, AR-V7, Androgen deprivation therapy, Targeted therapy, Oncogenic pathways

Superscan in First Posttherapeutic 177Lu-PSMA Scan.

This case highlights the effectiveness of 177Lu-PSMA therapy in a 70-year-old man with castration-resistant prostate cancer who has extensive skeletal metastases in posttherapeutic whole-body imaging. A 70-year-old man with extensive skeletal metastases underwent 4 cycles of 177 Lu-PSMA-617 therapy. A whole-body 177Lu-PSMA scan after the first cycle showed diffuse skeletal lesions, with minimal PSMA uptake in the kidneys and salivary glands. A whole-body scan after the fourth cycle of 177Lu-PSMA showed a complete response of skeletal metastases with normal PSMA uptake in the kidneys and salivary glands. According to RECİP 1.0, the patient was considered a complete response.

Formulating abiraterone acetate-HPMCAS-based amorphous solid dispersions: insights into in vitro and biorelevant dissolution assessments and pharmacokinetic evaluations.

Abiraterone acetate (ABTA) is used as a primary treatment for metastatic castration-resistant prostate cancer. Its low aqueous solubility results in inadequate dissolution and poor oral bioavailability (<10%), necessitating the consumption of large doses of ABTA (1000 mg per day) for desired efficacy. The aim of this study is to enhance the solubility, dissolution, and bioavailability of ABTA through amorphous solid dispersions (SDs). ABTA-SD was prepared via a solvent granulation method with different grades of hydroxypropyl methylcellulose acetate succinate (HPMCAS 716 and 912). The theoretical solubility parameter between ABTA and HPMCAS was below 7 MPa1/2, indicating miscibility between the drug and the polymer according to the Hansen solubility parameter. HPMCAS showed a remarkable recrystallization inhibition of up to 180 min compared to the free drug (10 min), maintaining the soluble drug in supersaturation state and exhibiting the "spring and parachute" phenomenon. ABTA-SD exhibited a higher solubility (1.16-fold to 52-fold) in different media than free ABTA. The results of DSC, PXRD, ATR-FTIR, and FE-SEM indicated that the crystallinity of ABTA was completely transformed to an amorphous form and maintained in the SD formulation. In vitro and bio-relevant dissolution behavior of ABTA was studied in various dissolution media, indicating the higher dissolution of ABTA-SD than that of free ABTA. The pharmacokinetic study conducted in Wistar rats revealed that C max and AUC0-t of the optimized ABTA-SD formulation were significantly enhanced by 1.92-fold and 2.87-fold, respectively, compared to those of free ABTA.

Multigene Copy Number Alteration Risk Score Biomarker-Based Enrichment Study Designs in Metastatic Castrate-Resistant Prostate Cancer.

A composite multigene risk score derived from tumor-biology alterations specific to metastatic castrate-resistant prostate cancer (mCRPC) state was evaluated as a classifier to design biomarker-based enrichment clinical trials. A plasma cell-free DNA copy number alteration risk score based on alterations in 24 genes was simulated to develop a biomarker classifier-based clinical trial design enriched for high-risk patients to detect a survival advantage of a novel treatment (hazard ratio of 0.70 with 80% power). We determined the design trade-offs between the number of patients screened and enrolled when varying the type of patients to enrich and the extent of enrichment needed. For a 2-year overall survival end point in mCRPC state, fully enriching patients with mCRPC having a high-risk score of 3 or more (the 95th percentile of a range of risk scores in patients with mCRPC) was determined to require screening to a maximum of 4,149 patients to enroll 259 patients for the targeted effect size. A nonenriched trial was determined to require enrolling 689 patients to be equivalently powered. We identified a pragmatic alternative, which is to enrich patients with mCRPC with a risk score of 1 or more (the 67th percentile) and an enrichment fraction of 0.25. This would require screening 658 patients to enroll 584 patients, and it maximizes the ability to detect a difference in treatment effect by risk score. A plasma multi-CNA risk score classifier can feasibly be leveraged to design an enrichment trial in mCRPC. Enriching 25% of patients screened with a risk score >1 was observed to be optimal for obtaining an adequately powered, biomarker-based mCRPC-enriched clinical trial.

PSMA Radiotheranostics in Prostate Cancer: Principles, Practice, and Future Prospects.

Prostate cancer is a leading cause of cancer-related mortality in men, with metastatic castration-resistant prostate cancer presenting a substantial treatment challenge. The authors focuse on prostate-specific membrane antigen (PSMA) radiotheranostics, particularly lutetium 177 (177Lu)-PSMA radioligand therapy, as an emerging treatment modality for metastatic castration-resistant prostate cancer. The U.S. Food and Drug Administration approval of 177Lu-PSMA-617 marked a substantial advancement in the treatment paradigm of metastatic castration-resistant prostate cancer, based on the VISION trial that showed improved overall survival and quality of life compared with those for standard care. PSMA expression, assessed via PSMA PET, is crucial for patient selection and assessment of treatment eligibility. The authors discuss current practices, including therapy administration, dosing, and side effects, with a particular focus on eligibility criteria and the added value of posttherapy imaging. Response assessment criteria using PSMA PET are discussed, although these require further validation. The discussion of future directions highlights ongoing trials investigating PSMA targeting agents, the extension of radioligand therapy to earlier stages of prostate cancer, and combination therapies. This review underscores the role of PSMA radioligand therapy in the evolving landscape of prostate cancer treatment and its promise for improving patient outcomes. ©RSNA, 2024 Supplemental material is available for this article.

Defining the Position of [177Lu]Lu-PSMA Radioligand Therapy in the Treatment Landscape of Metastatic Castration-Resistant Prostate Cancer: A Meta-analysis of Clinical Trials.

In recent years, theranostics has become a promising approach for treating metastatic castration-resistant prostate cancer (mCRPC), with trials investigating targeted radioligand therapy, particularly using prostate-specific membrane antigen labeled with lutetium-177 ([177Lu]Lu-PSMA). The proper position of [177Lu]Lu-PSMA in the therapeutic algorithm of mCRPC is yet to be identified. We conducted a systematic review and meta-analysis of phase II/III randomized controlled trials to assess the efficacy of [177Lu]Lu-PSMA in treating mCRPC. Study endpoints included radiographic progression-free survival (rPFS), prostate-specific antigen-PFS, objective response rate, and overall survival. Data were extracted according to the PRISMA statement. Summary hazard ratios (HRs) were calculated using random- or fixed-effects models. Statistical analyses were performed with RevMan software (v.5.2.3). [177Lu]Lu-PSMA reduced the risk of rPFS (HR 0.55; 95% confidence interval [CI] 0.43-0.71; p < 0.00001) and prostate-specific antigen-PFS (HR 0.53; 95% CI 0.41-0.67; p < 0.00001), and improved the objective response rate compared with control therapies (response rate 3.55; 95% CI 1.91-6.60; p < 0.0001), whereas no significant cumulative effect on overall survival was documented (HR 0.92; 95% CI 0.65-1.31; p = 0.63). Notably, in a dedicated subanalysis, comparable effects on rPFS were observed when [177Lu]Lu-PSMA was compared with active therapy. [177Lu]Lu-PSMA has a favorable impact on the radiographic and biochemical control of mCRPC and represents a potential treatment in a scenario where other valuable options are available. Further efforts are required to identify clinical and molecular markers necessary for proper patient stratification.

Dual-Tracer 18F-FDG and 68Ga-PSMA PET/CT Imaging of Heterogeneous Phenotypes of Metastatic Castration-Resistant Prostate Cancer for Predicting Response to Novel Hormone Therapy.

This study evaluated interlesion heterogeneity in prostate cancer using dual-tracer imaging (PSMA and FDG) and explored its predictive value for novel hormone therapy (NHT). A total of 205 prostate cancer patients (23 biochemical recurrences, 68 metastatic castration-sensitive prostate cancers, 114 metastatic castration-resistant prostate cancers [mCRPC]) who underwent dual 18F-FDG and 68Ga-PSMA PET/CT imaging were retrospectively analyzed. Among them, 62 mCRPC patients received NHT. Patients were classified into 3 groups: PSMA+FDG-, PSMA+FDG+, and PSMA-FDG+. SUVratio, the ratio of PSMA-SUVmax to FDG-SUVmax, was evaluated for its predictive value on progression-free survival (PFS). The proportion of PSMA+FDG- patients decreased from biochemical recurrence to mCRPC stages, whereas FDG+ cases increased significantly (P = 0.001). In the NHT cohort, group 3 (PSMA-FDG+) had significantly shorter median PFS than group 1 (133 vs 497 days; P = 0.027). In group 2, patients with a high SUVratio had better median PFS than those with a low SUVratio (368 vs 147 days; P = 0.031). Dual-tracer imaging reveals interlesion heterogeneity in prostate cancer, and SUVratio may help predict early response to NHT.

Framework for the Pathology Workup of Metastatic Castration-Resistant Prostate Cancer Biopsies.

Lineage plasticity and histologic transformation from prostate adenocarcinoma to neuroendocrine prostate cancer (NEPC) occurs in up to 15-20% of patients with castration-resistant prostate cancer (CRPC) as mechanism of treatment resistance and is associated with aggressive disease and poor prognosis. NEPC tumors typically display small cell carcinoma morphology with loss of androgen receptor (AR) expression and gain of neuroendocrine (NE) lineage markers. However, there is a spectrum of phenotypes that are observed during the lineage plasticity process, and the clinical significance of mixed histologies or those that co-express AR and NE markers or lack all markers is not well defined. Translational research studies investigating NEPC have used variable definitions making clinical trial design challenging. Here we discuss the diagnostic workup of metastatic biopsies to help guide the reproducible classification of phenotypic CRPC subtypes. We recommend classifying CRPC tumors based on histomorphology (adenocarcinoma, small cell carcinoma, poorly differentiated carcinoma, other morphologic variant, or mixed morphology) and immunohistochemical markers with a priority for AR, NKX3.1, INSM1, synaptophysin and cell proliferation based on Ki-67 positivity, with additional markers to be considered based on the clinical context. Ultimately, a unified workup of metastatic CRPC biopsies can improve clinical trial design and eventually practice.

Systematic literature review and meta-analysis of health state utility values in metastatic castration-resistant prostate cancer.

Despite being an important goal, the preservation of quality of life of patients with metastatic castration-resistant prostate cancer (mCRPC) is poorly characterized across lines of therapy. In this review, a systematic literature review and meta-analysis were conducted to synthesize EuroQoL 5-Dimension (EQ-5D) data among adult men with asymptomatic or mildly symptomatic mCRPC in both first line (1L) and second line and later (2L+) therapy. MEDLINE, Embase, and Cochrane CENTRAL were searched from inception to October 2022 using Ovid. Supplemental searches of other data sources were also conducted (PROSPERO registration: CRD42021283512). Meta-analyses were conducted to estimate pooled EQ-5D index utility values and EQ visual analog scale (VAS) scores in both 1L and 2L+. Various sensitivity analyses were also conducted. Forty-five unique publications met the inclusion criteria. In primary studies, baseline EQ-5D index utility values ranged from 0.7 to 0.9 in 1L and 0.63 to 0.7 in 2L+. Twelve trials and observational studies were feasible for inclusion in the meta-analysis. The pooled mean baseline EQ-5D index utility value was estimated as 0.79 (95% CI, 0.70-0.84) and 0.69 (95% CI, 0.67-0.71) for 1L (n = 7 studies) and 2L + (n = 4 studies), respectively. The pooled mean baseline EQ VAS score was estimated as 74.63 (95% CI, 70.97-78.29) and 65.82 (95% CI, 64.53-67.11) in 1L and 2L+, respectively. Limitations include hampered comparability between studies due to heterogeneity in study design and geographical regions. This study provides a comprehensive synthesis of EQ-5D data presently available in adults with mCRPC in both 1L and 2L + therapy.

GDF15 propeptide promotes bone metastasis of castration-resistant prostate cancer by augmenting the bone microenvironment

BackgroundBone metastasis (BM) is a common and fatal condition in patients with castration-resistant prostate cancer (CRPC). However, there are no useful blood biomarkers for CRPC with BM, and the mechanism underlying BM is unclear. In this study, we investigated precise blood biomarkers for evaluating BM that can improve the prognosis of patients with CRPC.MethodsWe comprehensively examined culture supernatants from four prostate cancer (PCa) cell lines using Orbitrap mass spectrometry to identify specific proteins secreted abundantly by PCa cells. The effects of this protein to PCa cells, osteoblasts, osteoclasts were examined, and BM mouse model. In addition, we measured the plasma concentration of this protein in CRPC patients for whom bone scan index (BSI) by bone scintigraphy was performed.ResultsA total of 2,787 proteins were identified by secretome analysis. We focused on GDF15 propeptide (GDPP), which is secreted by osteoblasts, osteoclasts, and PCa cells. GDPP promoted the proliferation, invasion, and migration of PC3 and DU145 CRPC cells, and GDPP aggravated BM in a mouse model. Importantly, GDPP accelerated bone formation and absorption in the bone microenvironment by enhancing the proliferation of osteoblasts and osteoclasts by upregulating individual transcription factors such as RUNX2, OSX, ATF4, NFATc1, and DC-STAMP. In clinical settings, including a total of 416 patients, GDPP was more diagnostic of BM than prostate-specific antigen (PSA) (AUC = 0.92 and 0.78) and the seven other blood biomarkers (alkaline phosphatase, lactate dehydrogenase, bone alkaline phosphatase, tartrate-resistant acid phosphatase 5b, osteocalcin, procollagen I N-terminal propeptide and mature GDF15) in patients with CRPC. The changes in BSI over time with systemic treatment were correlated with that of GDPP (r = 0.63) but not with that of PSA (r = -0.16).ConclusionsGDPP augments the tumor microenvironment of BM and is a novel blood biomarker of BM in CRPC, which could lead to early treatment interventions in patients with CRPC.

Talazoparib for the Treatment of Metastatic Castration-resistant Prostate Cancer

Breast and prostate cancer are among the most commonly diagnosed cancers worldwide. Recent advances in tumor sequencing and gene studies have led to a paradigm shift from treatment centered on the type of tumor to therapy more focused on specific immune phenotype markers and molecular alterations. In this review, we discuss the utility and function of talazoparib concerning prostate cancer treatment and summarize recent and planned clinical trials on talazoparib. We searched medical databases for articles relating to the use of talazoparib in prostate cancer from inception. Poly ADP ribose polymerase (PARP) is a family of 17 necessary DNA repair enzymes responsible for base excision repair, single-strand break repair, and double-strand break repair. PARP inhibitors are a class of oral targeted therapies that compete for the NAD+ binding site on PARP molecules. Talazoparib, a potent PARP inhibitor, has emerged as a significant therapeutic option in the treatment of metastatic castration-resistant prostate cancer (mCRPC), particularly for patients with specific genetic alterations. Its role as a PARP inhibitor makes it a targeted therapy, focusing on cancer cells with DNA repair deficiencies. Talazoparib’s role as a biomarker-directed therapy in advanced prostate cancer has been increasingly recognized. The TALAPRO-1 demonstrated durable antitumor activity in mCRPC patients. TALAPRO-2 is a notable clinical trial, specifically examining the effectiveness of Talazoparib when used in combination therapies. Current investigations demonstrate a significant improvement in survival outcomes for the patients of mCRPC, making Talazoparib a promising intervention.

Targeting Androgen Receptor Variants in Castration-Resistant Prostate Cancer (CRPC): A Comprehensive Review

Targeting Androgen Receptor Variants in Castration-Resistant Prostate Cancer (CRPC): A Comprehensive Review