prostate cancer progression

PURPOSE OF REVIEW: Our review delves into the progress across urological malignancies and discusses ongoing challenges and future directions in antibody-drug conjugate (ADC) development, emphasising their transformative potential in cancer care. RECENT FINDINGS: ADCs have advanced from hematologic to solid tumours, notably in breast cancer, and are now pivotal in metastatic urological cancers as both monotherapies and in combination regimens, underscored by the FDA's approval of enfortumab vedotin and sacituzumab govitecan for metastatic urothelial cancer...

Prostate cancer is a leading diagnosis and major cause of cancer-related deaths in men worldwide. As a typical hormone-responsive disease, prostate cancer is commonly managed with androgen deprivation therapy (ADT) to curb its progression and potential metastasis. Unfortunately, progression to castration-resistant prostate cancer (CRPC), a notably more aggressive phase of the disease, occurs within a timeframe of 2-3 years following ADT. Enzalutamide, a recognized androgen receptor (AR) antagonist, has been employed as a standard of care for men with metastatic castration-resistant prostate cancer (mCRPC) since it was first approved in 2012, due to its ability to prolong survival...

There is a long history of curative treatment of prostate cancer. However, as prostate cancer often grows very slowly, and symptoms do not have time to develop during a person's lifetime, a more tentative approach has become more and more common in many cases. This may be through either watchful waiting or active surveillance. In the first case palliative hormonal treatment is given in the case of progression, in the latter curative treatment would be the choice. When treatment is deemed necessary for localized disease, surgery and radiotherapy are considered equivalent in terms of efficacy and overall risk of side effects...

BACKGROUND: Stereotactic Ablative Radiotherapy (SABR) for the treatment of oligometastatic disease can improve survival and delay the requirement for systemic therapy. The benefits of SABR in oligoprogressive disease are less well-defined. Here, we evaluate the available evidence investigating the efficacy of SABR in the treatment of oligoprogressive disease. METHODS: A systematic review was carried out following PRISMA guidelines. Medline and Embase databases were searched using the terms "stereotactic radiotherapy" OR "SABR" OR "Stereotactic Ablative Body Radiotherapy" OR "SBRT" OR "SRT" AND "oligoprogression" in May 2022, June 2023, and February 2024...

Alteration of cell metabolism is one of the essential characteristics of tumor growth. Cancer stem cells (CSCs) are the initiating cells of tumorigenesis, proliferation, recurrence, and other processes, and play an important role in therapeutic resistance and metastasis. Thus, identification of the metabolic profiles in prostate cancer stem cells (PCSCs) is critical to understanding prostate cancer progression. Using untargeted metabolomics and lipidomics methods, we show distinct metabolic differences between prostate cancer cells and PCSCs...

A 74-year-old man was suffering from nine months of perineal pain and progressive worsening of urinary symptoms including nocturia and urgency. His prostate-specific antigen (PSA) levels were 1.48 ng/mL at the time of referral. Initially, a differential diagnosis of prostatitis or seminal vesicle inflammation was made, and four weeks of antibiotics were prescribed, which were later extended to six weeks due to failure of symptoms to resolve. Magnetic resonance imaging (MRI) of the prostate was then conducted...

Adenocarcinomas from multiple tissues can converge to treatment-resistant small cell neuroendocrine (SCN) cancers comprised of ASCL1, POU2F3, NEUROD1, and YAP1 subtypes. We investigated how mitochondrial metabolism influences SCN cancer (SCNC) progression. Extensive bioinformatics analyses encompassing thousands of patient tumors and human cancer cell lines uncovered enhanced expression of PGC-1α, a potent regulator of mitochondrial oxidative phosphorylation (OXPHOS), across several SCNC types. PGC-1α correlated tightly with increased expression of the lineage marker ASCL1 through a positive feedback mechanism...

Lineage plasticity is a recognized hallmark of cancer progression that can shape therapy outcomes. The underlying cellular and molecular mechanisms mediating lineage plasticity remain poorly understood. Here, we describe a versatile in vivo platform to identify and interrogate the molecular determinants of neuroendocrine lineage transformation at different stages of prostate cancer progression. Adenocarcinomas reliably develop following orthotopic transplantation of primary mouse prostate organoids acutely engineered with human-relevant driver alterations (e...

Genome wide association studies (GWASs) have identified numerous risk loci associated with prostate cancer, yet unraveling their functional significance remains elusive. Leveraging our high-throughput SNPs-seq method, we pinpointed rs4519489 within the multi-ancestry GWAS-discovered 2p25 locus as a potential functional SNP due to its significant allelic differences in protein binding. Here, we conduct a comprehensive analysis of rs4519489 and its associated gene, NOL10, employing diverse cohort data and experimental models...

UNLABELLED: Targeting cell surface molecules using radioligand and antibody-based therapies has yielded considerable success across cancers. However, it remains unclear how the expression of putative lineage markers, particularly cell surface molecules, varies in the process of lineage plasticity, wherein tumor cells alter their identity and acquire new oncogenic properties. A notable example of lineage plasticity is the transformation of prostate adenocarcinoma (PRAD) to neuroendocrine prostate cancer (NEPC)--a growing resistance mechanism that results in the loss of responsiveness to androgen blockade and portends dismal patient survival...

We analyzed genomic data derived from the prostate cancer of African and European American men in order to identify differences that may contribute to racial disparity of outcome and that could also define novel therapeutic strategies. In addition to analyzing patient derived next generation sequencing data, we performed FISH based confirmatory studies of Chromodomain helicase DNA-binding protein 1 ( CHD1 ) loss on prostate cancer tissue microarrays. We created CRISPR edited, CHD1 deficient prostate cancer cell lines for genomic, drug sensitivity and functional homologous recombination (HR) activity analysis...

Objective: To investigate the genetic and expression characteristics of transcription factor IIH (TFIIH) in pre-initiationcomplex in prostate cancer (PCa) and its relationship with prostate cancer progression. Methods: Analyzing the expression characteristics and clinical signification of TFIIH subunits about 495 cases of PCa and 52 cases of adjacent cancer in The Cancer Genome Atlas-Prostate adenocarcinoma (TCGA-PRAD) database. PCa microarray chip was used to verify the correlation between the key factor General Transcription Factor IIH Subunit 4 (GTF2H4) in TFIIH and clinical features...

BACKGROUND AND OBJECTIVE: Addition of darolutamide to androgen deprivation therapy (ADT) and docetaxel significantly improved overall survival (OS) in ARASENS (NCT02799602). Here we report on prostate-specific antigen (PSA) responses and their association with outcomes. METHODS: ARASENS is an international, double-blind, phase 3 study in patients with metastatic hormone-sensitive prostate cancer (mHSPC) randomized to darolutamide 600 mg orally twice daily (n = 651) or placebo (n = 654), both with ADT + docetaxel...

Prostate cancer causes numerous male deaths annually. Although great progress has been made in the diagnosis and treatment of prostate cancer during the past several decades, much about this disease remains unknown, especially its pathobiology. The kinesin superfamily is a pivotal group of motor proteins, that contains a microtubule-based motor domain and features an adenosine triphosphatase activity and motility characteristics. Large-scale sequencing analyses based on clinical samples and animal models have shown that several members of the kinesin family are dysregulated in prostate cancer...

BACKGROUND: The critical role of radiographic assessment at the time of castration-resistant prostate cancer (CRPC) diagnosis is underscored by this study. We performed a retrospective analysis of radiographic changes in metastasis from the time of diagnosis of metastatic hormone-sensitive prostate cancer (mHSPC) to CRPC diagnosis. We also explored its impact on prognosis post-CRPC. MATERIALS AND METHODS: We retrospectively analyzed 98 men who underwent radiographic examinations (bone scans and computed tomography [CT]) at the time of CRPC diagnosis...

A dual-targeting approach is predicted to yield better cancer therapy outcomes. Consequently, a series of coumarin-based thiazoles ( 5a - h , 6 , and 7a - e ) were designed and constructed as potential carbonic anhydrase (CA) and VEGFR-2 suppressors. The inhibitory actions of the target compounds were assessed against CA isoforms IX and VEGFR-2. The assay results showed that coumarin-based thiazoles 5a , 5d , and 5e can effectively inhibit both targets. 5a , 5d , and 5e cytotoxic effects were tested on pancreatic, breast, and prostate cancer cells (PANC1, MCF7, and PC3)...

BACKGROUND: Poly ADP-ribose polymerase (PARP) inhibitors are approved for the treatment of some men with advanced prostate cancer. Rare but serious side effects include myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). The impact of PARP inhibitors on clonal hematopoiesis (CH), a potential precursor lesion associated with MDS and AML, is incompletely understood in prostate cancer. We hypothesized that PARP inhibitors would increase CH prevalence and abundance. METHODS: We prospectively enrolled participants with advanced prostate cancer treated with PARP inhibitors...

The androgen receptor (AR) and estrogen receptor alpha (ERα) are steroid receptor transcription factors with critical roles in the development and progression of prostate and breast cancers. Advances in the understanding of mechanisms underlying the ligand-dependent activation of these transcription factors have contributed to the development of small molecule inhibitors that block AR and ERα actions. These inhibitors include competitive antagonists and degraders that directly bind the ligand binding domains of these receptors, luteinizing hormone releasing hormone (LHRH) analogs that suppress gonadal synthesis of testosterone or estrogen, and drugs that block specific enzymes required for biosynthesis of testosterone or estrogen...

With the rise of precision medicine, the continuous expansionWith the rise of precision medicine, the continuous expansion the collective push from many other the application of Artificial Intelligence (AI) in prostate cancer diagnosis is increasingly becoming a focal point. AI technology can effectively utilize diverse detection methods such as Magnetic Resonance Imaging (MRI), Positron Emission Tomography (PET), and whole pathology slide imaging to efficiently identify and differentiate between benign and malignant lesions...

Recurrence, metastasis and drug resistance in patients with prostate cancer (PCa) are still important causes of high mortality in patients. Two important features of solid tumors, including PCa, are tumor angiogenesis and the emergence of cancer stemness. Studies have found that cancer stem cells can promote tumor angiogenesis, and the highly vascularized tumor microenvironment further supports the growth of these stem cells, forming a harmful cycle that leads to tumor recurrence, metastasis, and drug resistance...