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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 -
Genes & Development Sep 2018Despite the high long-term survival in localized prostate cancer, metastatic prostate cancer remains largely incurable even after intensive multimodal therapy. The... (Review)
Review
Despite the high long-term survival in localized prostate cancer, metastatic prostate cancer remains largely incurable even after intensive multimodal therapy. The lethality of advanced disease is driven by the lack of therapeutic regimens capable of generating durable responses in the setting of extreme tumor heterogeneity on the genetic and cell biological levels. Here, we review available prostate cancer model systems, the prostate cancer genome atlas, cellular and functional heterogeneity in the tumor microenvironment, tumor-intrinsic and tumor-extrinsic mechanisms underlying therapeutic resistance, and technological advances focused on disease detection and management. These advances, along with an improved understanding of the adaptive responses to conventional cancer therapies, anti-androgen therapy, and immunotherapy, are catalyzing development of more effective therapeutic strategies for advanced disease. In particular, knowledge of the heterotypic interactions between and coevolution of cancer and host cells in the tumor microenvironment has illuminated novel therapeutic combinations with a strong potential for more durable therapeutic responses and eventual cures for advanced disease. Improved disease management will also benefit from artificial intelligence-based expert decision support systems for proper standard of care, prognostic determinant biomarkers to minimize overtreatment of localized disease, and new standards of care accelerated by next-generation adaptive clinical trials.
Topics: Animals; Drug Resistance, Neoplasm; Gene Fusion; Humans; Male; Mice; Neoplasm Metastasis; Prognosis; Prostate; Prostatic Neoplasms; Tumor Microenvironment
PubMed: 30181359
DOI: 10.1101/gad.315739.118 -
Advances in Experimental Medicine and... 2018This chapter provides a brief overview of prostate cancer statistics, grading, diagnosis and treatment strategies that are discussed in more detail in the subsequent... (Review)
Review
This chapter provides a brief overview of prostate cancer statistics, grading, diagnosis and treatment strategies that are discussed in more detail in the subsequent chapters of this book and the companion book titled "Clinical Molecular and Diagnostic Imaging of Prostate Cancer and Treatment Strategies". It also points to websites that provide additional useful information for patients affected by prostate cancer and for students and teachers to obtain practical and updated information on research, new diagnostic modalities and new therapies including new updated clinical trials. Three sections are focused on overview of prostate cancer statistics; overview of detection, diagnosis, stages and grading of prostate cancer; and treatment possibilities and options.
Topics: Humans; Male; Neoplasm Grading; Prostatic Neoplasms
PubMed: 30229546
DOI: 10.1007/978-3-319-95693-0_1 -
Nature Reviews. Disease Primers Feb 2021Prostate cancer is a complex disease that affects millions of men globally, predominantly in high human development index regions. Patients with localized disease at a... (Review)
Review
Prostate cancer is a complex disease that affects millions of men globally, predominantly in high human development index regions. Patients with localized disease at a low to intermediate risk of recurrence generally have a favourable outcome of 99% overall survival for 10 years if the disease is detected and treated at an early stage. Key genetic alterations include fusions of TMPRSS2 with ETS family genes, amplification of the MYC oncogene, deletion and/or mutation of PTEN and TP53 and, in advanced disease, amplification and/or mutation of the androgen receptor (AR). Prostate cancer is usually diagnosed by prostate biopsy prompted by a blood test to measure prostate-specific antigen levels and/or digital rectal examination. Treatment for localized disease includes active surveillance, radical prostatectomy or ablative radiotherapy as curative approaches. Men whose disease relapses after prostatectomy are treated with salvage radiotherapy and/or androgen deprivation therapy (ADT) for local relapse, or with ADT combined with chemotherapy or novel androgen signalling-targeted agents for systemic relapse. Advanced prostate cancer often progresses despite androgen ablation and is then considered castration-resistant and incurable. Current treatment options include AR-targeted agents, chemotherapy, radionuclides and the poly(ADP-ribose) inhibitor olaparib. Current research aims to improve prostate cancer detection, management and outcomes, including understanding the fundamental biology at all stages of the disease.
Topics: Androgen Antagonists; Humans; Male; Neoplasm Recurrence, Local; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms
PubMed: 33542230
DOI: 10.1038/s41572-020-00243-0 -
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 -
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 -
Critical Reviews in Oncology/hematology Jan 2022Overweight and obese men with prostate cancer are at an increased risk of disease recurrence, exacerbated treatment-related adverse effects, development of... (Review)
Review
Overweight and obese men with prostate cancer are at an increased risk of disease recurrence, exacerbated treatment-related adverse effects, development of obesity-related comorbidities, earlier progression and development of metastatic disease, and higher all-cause and prostate cancer-specific mortality. The physiological mechanisms associating obesity with poor prostate cancer outcomes remain largely unknown; however, an increased inflammatory environment and metabolic irregularities associated with excess fat mass are commonly postulated. Although research is limited, fat loss strategies using exercise and nutrition programmes may slow down prostate cancer progression and improve a patient's prognosis. This review is an overview of: 1) the association between obesity and poor prostate cancer prognosis; 2) potential physiological mechanisms linking obesity and prostate cancer progression; 3) the effect of obesity on treatments for prostate cancer; and 4) the potential for weight loss strategies to improve outcomes in patients with prostate cancer.
Topics: Body Mass Index; Exercise; Humans; Male; Neoplasm Recurrence, Local; Obesity; Overweight; Prostatic Neoplasms
PubMed: 34808374
DOI: 10.1016/j.critrevonc.2021.103543 -
Archivos Espanoles de Urologia Mar 2018Prostate cancer is a disease that presents a wide spectrum from low aggressiveness localized to disseminated cancer. Locally advanced prostate cancer (LAPC) is a... (Review)
Review
UNLABELLED
Prostate cancer is a disease that presents a wide spectrum from low aggressiveness localized to disseminated cancer. Locally advanced prostate cancer (LAPC) is a particularly difficult to manage phase of this spectrum.
OBJECTIVES
We review the definition, diagnosis and treatment of this phase of the disease.
METHODS
We performed a non systematic literature review of the most relevant features of this pathology.
RESULTS
LAPC is more aggressive than organ confined disease. Its clinical diagnosis is not always easy. Local treatment, in spite of being aggressive with potential sequelae, seems to be advantageous in terms of patient survival.
CONCLUSIONS
Prostate cancer local staging is currently based on multiparametric magnetic resonance imaging (mpMRI). Local radical treatment with surgery or radiotherapy, with probable addition of systemic treatment, offers promising results for disease control and quality of life improvement.
Topics: Humans; Male; Neoplasm Staging; Prostatic Neoplasms
PubMed: 29633943
DOI: No ID Found -
Missouri Medicine 2018Prostate cancer is common, and recent efforts in clinical management have focused on identifying patients who could be candidates from less aggressive management or who... (Review)
Review
Prostate cancer is common, and recent efforts in clinical management have focused on identifying patients who could be candidates from less aggressive management or who could benefit from more aggressive therapy. As prostate cancer histology, especially Gleason score, plays a critical role in predicting patient outcomes, attempts have been made to refine histologic classification and reporting in prostate cancer to facilitate patient risk stratification. This review discusses recent updates in prostate cancer grading and reporting.
Topics: Biopsy; Humans; Male; Neoplasm Grading; Prognosis; Prostate; Prostatic Neoplasms
PubMed: 30228708
DOI: No ID Found -
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