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Molecules (Basel, Switzerland) Sep 2022Prostate cancer is one of the malignancies that affects men and significantly contributes to increased mortality rates in men globally. Patients affected with prostate... (Review)
Review
Prostate cancer is one of the malignancies that affects men and significantly contributes to increased mortality rates in men globally. Patients affected with prostate cancer present with either a localized or advanced disease. In this review, we aim to provide a holistic overview of prostate cancer, including the diagnosis of the disease, mutations leading to the onset and progression of the disease, and treatment options. Prostate cancer diagnoses include a digital rectal examination, prostate-specific antigen analysis, and prostate biopsies. Mutations in certain genes are linked to the onset, progression, and metastasis of the cancer. Treatment for localized prostate cancer encompasses active surveillance, ablative radiotherapy, and radical prostatectomy. Men who relapse or present metastatic prostate cancer receive androgen deprivation therapy (ADT), salvage radiotherapy, and chemotherapy. Currently, available treatment options are more effective when used as combination therapy; however, despite available treatment options, prostate cancer remains to be incurable. There has been ongoing research on finding and identifying other treatment approaches such as the use of traditional medicine, the application of nanotechnologies, and gene therapy to combat prostate cancer, drug resistance, as well as to reduce the adverse effects that come with current treatment options. In this article, we summarize the genes involved in prostate cancer, available treatment options, and current research on alternative treatment options.
Topics: Androgen Antagonists; Humans; Male; Neoplasm Recurrence, Local; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Salvage Therapy
PubMed: 36080493
DOI: 10.3390/molecules27175730 -
Nature Reviews. Urology Feb 2021From a clinical, morphological and molecular perspective, prostate cancer is a heterogeneous disease. Primary prostate cancers are often multifocal, having... (Review)
Review
From a clinical, morphological and molecular perspective, prostate cancer is a heterogeneous disease. Primary prostate cancers are often multifocal, having topographically and morphologically distinct tumour foci. Sequencing studies have revealed that individual tumour foci can arise as clonally distinct lesions with no shared driver gene alterations. This finding demonstrates that multiple genomically and phenotypically distinct primary prostate cancers can be present in an individual patient. Lethal metastatic prostate cancer seems to arise from a single clone in the primary tumour but can exhibit subclonal heterogeneity at the genomic, epigenetic and phenotypic levels. Collectively, this complex heterogeneous constellation of molecular alterations poses obstacles for the diagnosis and treatment of prostate cancer. However, advances in our understanding of intra-tumoural heterogeneity and the development of novel technologies will allow us to navigate these challenges, refine approaches for translational research and ultimately improve patient care.
Topics: Biomarkers, Tumor; Epigenesis, Genetic; Genetic Heterogeneity; Genome; Genomics; Humans; Male; Neoplasm Metastasis; Neoplasms, Multiple Primary; Phenotype; Prostatic Neoplasms; Prostatic Neoplasms, Castration-Resistant; Treatment Outcome
PubMed: 33328650
DOI: 10.1038/s41585-020-00400-w -
Current Oncology Reports Jan 2021Neuroendocrine prostate cancer (NEPC) is an aggressive histologic subtype of prostate cancer that most commonly arises in later stages of prostate cancer as a mechanism... (Review)
Review
PURPOSE OF REVIEW
Neuroendocrine prostate cancer (NEPC) is an aggressive histologic subtype of prostate cancer that most commonly arises in later stages of prostate cancer as a mechanism of treatment resistance. The poor prognosis of NEPC is attributed in part to late diagnosis and a lack of effective therapeutic agents. Here, we review the clinical and molecular features of NEPC based on recent studies and outline future strategies and directions.
RECENT FINDINGS
NEPC can arise "de novo" but most commonly develops as a result of lineage plasticity whereby prostate cancer cells adopt alternative lineage programs as a means to bypass therapy. Dependence on androgen receptor (AR) signaling is lost as tumors progress from a prostate adenocarcinoma to a NEPC histology, typically manifested by the downregulation of AR, PSA, and PSMA expression in tumors. Genomic analyses from patient biopsies combined with preclinical modeling have pointed to loss of tumor suppressors RB1 and TP53 as key facilitators of lineage plasticity. Activation of oncogenic drivers combined with significant epigenetic changes (e.g., EZH2 overexpression, DNA methylation) further drives tumor proliferation and expression of downstream neuronal and neuroendocrine lineage pathways controlled in part by pioneer and lineage determinant transcription factors (e.g., SOX2, ASCL1, BRN2). These biologic insights have provided a framework for the study of this subgroup of advanced prostate cancers and have started to provide rationale for the development of biomarker-driven therapeutic strategies. Further study of the dynamic process that leads to NEPC is required for the development of effective strategies to identify and treat patients developing lineage plasticity as a mechanism of treatment resistance.
Topics: Carcinoma, Neuroendocrine; Disease Progression; Drug Resistance, Neoplasm; Humans; Male; Prostatic Neoplasms
PubMed: 33433737
DOI: 10.1007/s11912-020-01003-9 -
International Journal of Molecular... Apr 2021Prostate cancer (PCa) is globally the second most diagnosed cancer type and the most common cause of cancer-related deaths in men. Family history of PCa, hereditary... (Review)
Review
Prostate cancer (PCa) is globally the second most diagnosed cancer type and the most common cause of cancer-related deaths in men. Family history of PCa, hereditary breast and ovarian cancer (HBOC) and Lynch syndromes (LS), are among the most important risk factors compared to age, race, ethnicity and environmental factors for PCa development. Hereditary prostate cancer (HPCa) has the highest heritability of any major cancer in men. The proportion of PCa attributable to hereditary factors has been estimated in the range of 5-15%. To date, the genes more consistently associated to HPCa susceptibility include mismatch repair (MMR) genes (, , , and ) and homologous recombination genes (, , , ). Additional genes are also recommended to be integrated into specific research, including , and . Importantly, and mutated patients potentially benefit from Poly (ADP-ribose) polymerase PARP inhibitors, through a mechanism of synthetic lethality, causing selective tumor cell cytotoxicity in cell lines. Moreover, the detection of germline alterations in MMR genes has therapeutic implications, as it may help to predict immunotherapy benefits. Here, we discuss the current knowledge of the genetic basis for inherited predisposition to PCa, the potential target therapy, and the role of active surveillance as a management strategy for patients with low-risk PCa. Finally, the current PCa guideline recommendations are reviewed.
Topics: Germ-Line Mutation; Humans; Male; Molecular Targeted Therapy; Neoplasm Proteins; Prostatic Neoplasms
PubMed: 33916521
DOI: 10.3390/ijms22073753 -
American Society of Clinical Oncology... Apr 2022Biochemical recurrence develops in almost one-third of men with prostate cancer after treatment with local therapy. There are numerous options for management, including... (Review)
Review
Biochemical recurrence develops in almost one-third of men with prostate cancer after treatment with local therapy. There are numerous options for management, including surveillance, salvage radiation, androgen deprivation therapy (ADT), and clinical trials. This article reviews the current approaches to radiation therapy, ADT, and molecular imaging in men with biochemically recurrent prostate cancer. First, radiation therapy, including selection of field, dose, and use of concurrent antiandrogen therapy, is reviewed. Next, molecular imaging is addressed, including prostate-specific membrane antigen PET imaging and its increased sensitivity in identifying sites of disease. Finally, the factors associated with starting ADT are explored, and the data supporting intermittent over continuous ADT are reviewed. Lastly, the use of prostate-specific membrane antigen PET imaging and its potential role influencing therapy are discussed.
Topics: Androgen Antagonists; Combined Modality Therapy; Humans; Male; Neoplasm Recurrence, Local; Positron-Emission Tomography; Prostate-Specific Antigen; Prostatic Neoplasms; Salvage Therapy
PubMed: 35503984
DOI: 10.1200/EDBK_351033 -
MMWR. Morbidity and Mortality Weekly... Oct 2020Among U.S. men, prostate cancer is the second leading cause of cancer-related death (1). Past studies documented decreasing incidence of prostate cancer overall since...
Among U.S. men, prostate cancer is the second leading cause of cancer-related death (1). Past studies documented decreasing incidence of prostate cancer overall since 2000 but increasing incidence of distant stage prostate cancer (i.e., signifying spread to parts of the body remote from the primary tumor) starting in 2010 (2,3). Past studies described disparities in prostate cancer survival by stage, age, and race/ethnicity using data covering ≤80% of the U.S. population (4,5). To provide recent data on incidence and survival of prostate cancer in the United States, CDC analyzed data from population-based cancer registries that contribute to U.S. Cancer Statistics (USCS).* Among 3.1 million new cases of prostate cancer recorded during 2003-2017, localized, regional, distant, and unknown stage prostate cancer accounted for 77%, 11%, 5%, and 7% of cases, respectively, but the incidence of distant stage prostate cancer significantly increased during 2010-2017. During 2001-2016, 10-year relative survival for localized stage prostate cancer was 100%. Overall, 5-year survival for distant stage prostate cancer improved from 28.7% during 2001-2005 to 32.3% during 2011-2016; for the period 2001-2016, 5-year survival was highest among Asian/Pacific Islanders (API) (42.0%), followed by Hispanics (37.2%), American Indian/Alaska Natives (AI/AN) (32.2%), Black men (31.6%), and White men (29.1%). Understanding incidence and survival differences by stage, race/ethnicity, and age can guide public health planning related to screening, treatment, and survivor care. Future research into differences by stage, race/ethnicity, and age could inform interventions aimed at improving disparities in outcomes.
Topics: Aged; Aged, 80 and over; Ethnicity; Humans; Incidence; Male; Middle Aged; Neoplasm Staging; Prostatic Neoplasms; Racial Groups; Survival Analysis; United States
PubMed: 33056955
DOI: 10.15585/mmwr.mm6941a1 -
Cancer Letters Oct 2021The treatment landscape of metastatic prostate cancer has evolved significantly over the past two decades. Several landmark phase 3 trials led to new drug approvals and... (Review)
Review
The treatment landscape of metastatic prostate cancer has evolved significantly over the past two decades. Several landmark phase 3 trials led to new drug approvals and rapid changes in therapy options for patients, including drugs with distinct mechanisms of action (e.g., hormonal, chemotherapy, radionuclide, immunotherapy, and targeted therapies). Therapies initially developed in later stages of the disease (metastatic castration resistant prostate cancer) have started to move earlier in the prostate cancer continuum, with new standards of care for metastatic hormone naive prostate cancer and non-metastatic castration resistant prostate cancer. Overall, patients are living longer with a better quality of life. However, despite these significant advances, prostate cancer remains a leading cause of cancer death globally. Disease heterogeneity and the emergence of therapy resistance remain significant barriers, and the identification and application of molecular biomarkers to guide the choice and sequencing of systemic agents are still in early stages. Here we discuss the current treatment landscape of metastatic prostate cancer, clinical challenges, and the emerging role of molecular biomarkers for targeting biologic subsets of advanced disease and co-targeting heterogenous resistance patterns.
Topics: Biomarkers, Tumor; Clinical Trials, Phase III as Topic; Drug Resistance, Neoplasm; Humans; Male; Prostatic Neoplasms; Quality of Life
PubMed: 34153403
DOI: 10.1016/j.canlet.2021.06.010 -
Cancer Letters Jan 2022Growing bodies of evidence have demonstrated that the identification of prostate cancer (PCa) biomarkers in the patients' blood and urine may remarkably improve PCa... (Review)
Review
Growing bodies of evidence have demonstrated that the identification of prostate cancer (PCa) biomarkers in the patients' blood and urine may remarkably improve PCa diagnosis and progression monitoring. Among diverse cancer-derived circulating materials, extracellular RNA molecules (exRNAs) represent a compelling component to investigate cancer-related alterations. Once outside the intracellular environment, exRNAs circulate in biofluids either in association with protein complexes or encapsulated inside extracellular vesicles (EVs). Notably, EV-associated RNAs (EV-RNAs) were used for the development of several assays (such as the FDA-approved Progensa Prostate Cancer Antigen 3 (PCA3 test) aiming at improving early PCa detection. EV-RNAs encompass a mixture of species, including small non-coding RNAs (e.g. miRNA and circRNA), lncRNAs and mRNAs. Several methods have been proposed to isolate EVs and relevant RNAs, and to perform RNA-Seq studies to identify potential cancer biomarkers. However, EVs in the circulation of a cancer patient include a multitude of diverse populations that are released by both cancer and normal cells from different tissues, thereby leading to a heterogeneous EV-RNA-associated transcriptional signal. Decrypting the complexity of such a composite signal is nowadays the major challenge faced in the identification of specific tumor-associated RNAs. Multiple deconvolution algorithms have been proposed so far to infer the enrichment of cancer-specific signals from gene expression data. However, novel strategies for EVs sorting and sequencing of RNA associated to single EVs populations will remarkably facilitate the identification of cancer-related molecules. Altogether, the studies summarized here demonstrate the high potential of using EV-RNA biomarkers in PCa and highlight the urgent need of improving technologies and computational approaches to characterize specific EVs populations and their relevant RNA cargo.
Topics: Antigens, Neoplasm; Biomarkers, Tumor; Cell-Free Nucleic Acids; Extracellular Vesicles; Gene Expression Regulation, Neoplastic; Humans; Male; MicroRNAs; Prostatic Neoplasms; RNA-Seq
PubMed: 34656688
DOI: 10.1016/j.canlet.2021.10.011 -
Pathologica Feb 2022In 2022, after a six-year interval, the International Agency for Research on Cancer (IARC) has published the 5th edition of the WHO Classification of Urinary and Male... (Review)
Review
In 2022, after a six-year interval, the International Agency for Research on Cancer (IARC) has published the 5th edition of the WHO Classification of Urinary and Male Genital Tumors, which provides a comprehensive update on tumor classification of the genitourinary system. This review article focuses on prostate carcinoma and underscores changes in the prostate chapter as well as those made across the entire series of the 5th edition of WHO Blue Books. Although no major alterations were made to this chapter, some of the most notable updates include restructure of contents and introduction of a new format; standardization of mitotic counts, genomic nomenclatures, and units of length; refined definition for the terms "variant", "subtype", and "histologic pattern"; reclassification of prostatic intraepithelial neoplasia (PIN)-like adenocarcinoma as a subtype of prostatic acinar adenocarcinoma; and recognition of treatment-related neuroendocrine prostatic carcinoma as a distinct tumor type. Evolving and unsettled issues related to grading of intraductal carcinoma of the prostate and reporting of tertiary Gleason pattern, the definition and prognostic significance of cribriform growth pattern, and molecular pathology of prostate cancer will also be covered in this review.
Topics: Humans; Male; Prostate; Prostatic Neoplasms; Adenocarcinoma; Prognosis; World Health Organization; Neoplasm Grading
PubMed: 36645399
DOI: 10.32074/1591-951X-822 -
Annals of Oncology : Official Journal... Sep 2020
Topics: Europe; Follow-Up Studies; Humans; Male; Neoplasm Staging; Prostate-Specific Antigen; Prostatic Neoplasms; Radiotherapy; Treatment Outcome
PubMed: 32593798
DOI: 10.1016/j.annonc.2020.06.011