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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 -
The Journal of Clinical Investigation Apr 2020Recent findings have shown that inhibitors targeting bromodomain and extraterminal domain (BET) proteins, such as the small molecule JQ1, are potent growth inhibitors of...
Recent findings have shown that inhibitors targeting bromodomain and extraterminal domain (BET) proteins, such as the small molecule JQ1, are potent growth inhibitors of many cancers and hold promise for cancer therapy. However, some reports have also revealed that JQ1 can activate additional oncogenic pathways and may affect epithelial-to-mesenchymal transition (EMT). Therefore, it is important to address the potential unexpected effect of JQ1 treatment, such as cell invasion and metastasis. Here, we showed that in prostate cancer, JQ1 inhibited cancer cell growth but promoted invasion and metastasis in a BET protein-independent manner. Multiple invasion pathways including EMT, bone morphogenetic protein (BMP) signaling, chemokine signaling, and focal adhesion were activated by JQ1 to promote invasion. Notably, JQ1 induced upregulation of invasion genes through inhibition of Forkhead box protein A1 (FOXA1), an invasion suppressor in prostate cancer. JQ1 directly interacted with FOXA1 and inactivated FOXA1 binding to its interacting repressors TLE3, HDAC7, and NFIC, thereby blocking FOXA1-repressive function and activating the invasion genes. Our findings indicate that JQ1 has an unexpected effect of promoting invasion in prostate cancer. Thus, the ill effect of JQ1 or its derived therapeutic agents cannot be ignored during cancer treatment, especially in FOXA1-related cancers.
Topics: Animals; Azepines; Epithelial-Mesenchymal Transition; Hepatocyte Nuclear Factor 3-alpha; Humans; Male; Mice; Mice, SCID; Neoplasm Invasiveness; Neoplasm Proteins; PC-3 Cells; Prostatic Neoplasms; Proteins; Triazoles; Xenograft Model Antitumor Assays
PubMed: 31874106
DOI: 10.1172/JCI126327 -
Abdominal Radiology (New York) Jul 2020Accurate early detection of recurrent prostate cancer after surgical or nonsurgical treatment is increasingly relevant in the era of evolving options for salvage... (Review)
Review
Accurate early detection of recurrent prostate cancer after surgical or nonsurgical treatment is increasingly relevant in the era of evolving options for salvage therapy. The importance of differentiating between local tumor recurrence, distant metastatic disease, and a combination of both in a patient with biochemical recurrence of prostate cancer is essential for appropriate treatment selection. Magnetic resonance imaging (MRI) is the best test for localization and characterization of locally residual or recurrent prostate cancer. It is essential for the radiologist involved in prostate MRI interpretation to be familiar with key imaging findings and advantages of different sequences to reach a confident diagnosis in the post-treatment setting. In this pictorial review, we present imaging findings of post-treatment prostate MRI including expected post-treatment anatomy and imaging characteristics, and the typical appearances of local tumor recurrence after radical prostatectomy, radiation therapy, and focal therapy for prostate cancer. While a multi-parametric MRI approach remains key just as in the treatment-naïve gland, this review emphasizes the much greater importance of the dynamic contrast-enhanced MRI sequence for evaluation in the post-treatment setting.
Topics: Humans; Magnetic Resonance Imaging; Male; Neoplasm Recurrence, Local; Prostate; Prostatectomy; Prostatic Neoplasms; Retrospective Studies
PubMed: 31788708
DOI: 10.1007/s00261-019-02348-x -
World Journal of Urology Dec 2019To review the current understanding and recent developments regarding the concept of oligometastases in hormone-sensitive prostate cancer.
PURPOSE
To review the current understanding and recent developments regarding the concept of oligometastases in hormone-sensitive prostate cancer.
METHODS
A comprehensive literature search of electronic databases, including PubMed and Embase was conducted for the search term 'oligometastases' in combinations with 'prostate cancer', 'hormone sensitive', 'genetics', and 'molecular'. All articles relating to these search terms have been taken into account.
RESULTS
Prostate cancer remains a major cause of morbidity and mortality worldwide. The majority of these cancer-related deaths result from metastases. Currently, there is a dichotomy in prostate cancer management where it is only deemed curable if it is localized, while any signs of metastasis relegate patients to systemic therapies to delay their inevitable death. A growing body of evidence supports the notion that aggressive treatments during the stable 'oligometastatic' state can have significant clinical benefits and potentially 'reset' prostate cancer to an earlier time point in cancer progression. This concept of oligometastases has been adopted in other cancer settings such as colorectal and non-small-cell lung cancers.
CONCLUSION
Multiple clinical and molecular biological studies have been influential in the support of a stable state in metastatic cancer progression coined 'oligometastases'. As our understanding of oligometastases in hormone-sensitive prostate cancer develops, we will be able to molecularly define the oligometastatic state and develop clinically available diagnostic tests. In doing so, prostate cancer patients will experience significant clinical benefits and the burden of prostate cancer worldwide will likely be reduced.
Topics: Androgen Antagonists; Humans; Male; Neoplasm Metastasis; Prostatic Neoplasms
PubMed: 30382379
DOI: 10.1007/s00345-018-2542-x -
International Journal of Molecular... Oct 2021This Special Issue focuses on the molecular mechanisms involved in therapeutic resistance, lineage plasticity, and phenotypic reprogramming leading to prostate cancer...
This Special Issue focuses on the molecular mechanisms involved in therapeutic resistance, lineage plasticity, and phenotypic reprogramming leading to prostate cancer recurrence and, ultimately, lethal disease [...].
Topics: Androgen Receptor Antagonists; Androgens; Drug Resistance, Neoplasm; Humans; Male; Neoplasm Recurrence, Local; Prostate; Prostatic Neoplasms; Receptors, Androgen; Signal Transduction
PubMed: 34769075
DOI: 10.3390/ijms222111645 -
Clinical Nuclear Medicine Nov 2021A 73-year-old man with history of grade group 1/Gleason 3 + 3 = 6 prostate adenocarcinoma status post prostatectomy had subsequent biochemical recurrence with serum...
A 73-year-old man with history of grade group 1/Gleason 3 + 3 = 6 prostate adenocarcinoma status post prostatectomy had subsequent biochemical recurrence with serum prostate-specific antigen level of 2.4 ng/mL. He underwent an 18F-fluciclovine PET/CT scan that demonstrated a left prostate bed recurrence and an incidental 18F-fluciclovine-avid smooth-edged solitary lung nodule with internal fat attenuation. Such uptake of 18F-fluciclovine in a lung hamartoma could be mistaken for prostate cancer metastasis. Given the increasing use of advanced imaging for prostate cancer, there is need for the imaging specialist to know about pitfalls and how to interpret them.
Topics: Aged; Carboxylic Acids; Cyclobutanes; Hamartoma; Humans; Male; Neoplasm Recurrence, Local; Positron Emission Tomography Computed Tomography; Prostatectomy; Prostatic Neoplasms
PubMed: 34582137
DOI: 10.1097/RLU.0000000000003672 -
Archivos Espanoles de Urologia Mar 2022Prostate cancer is themost prevalent and deadliest neoplasm in men, with adiverse clinical presentantion and oncological outcomes.The diagnosis and treatment remains a... (Review)
Review
INTRODUCTION
Prostate cancer is themost prevalent and deadliest neoplasm in men, with adiverse clinical presentantion and oncological outcomes.The diagnosis and treatment remains a challenge.New essays about biomarkers show their potential asa tool that may influence in clinical decision making,risk stratification and management of the disease.
METHODS
we performed a literature review abouttissue biomarkers in the diagnosis and treatment ofprostate cancer.
RESULTS
Within the last years, a wide number ofdiagnostic and prognostic tests in tissue have been developed(ConfirmMDx, Promark, Oncoytype DX, Decipher),creating an opportunity to improve the diagnosis,prognosis and treatment of prostate cancer.
CONCLUSIONS
Since prostate cancer is the mostprevalent neoplasm in men, it is mandatory to stratifypatients correctly to prevent unnecessary biopsiesand overtreatment in low risk patients, as well as designthe best strategy in those with high risk disease.Tissue biomarkers may become a useful tool in precisionmedicine to guide decision making.
Topics: Biomarkers, Tumor; Clinical Decision-Making; Humans; Male; Prognosis; Prostatic Neoplasms
PubMed: 35332888
DOI: No ID Found -
International Journal of Radiation... Nov 2022Prostate cancer ranges from localized, low risk to metastatic, morbid disease. Although radiation therapy (RT) is commonly incorporated in the treatment of early disease... (Review)
Review
Prostate cancer ranges from localized, low risk to metastatic, morbid disease. Although radiation therapy (RT) is commonly incorporated in the treatment of early disease or for palliation of symptomatic lesions, its role in extending survival in metastatic disease is less well-established. Here, we review the available evidence surrounding localized RT in the presence of oligometastatic disease and metastasis-directed therapy in both hormone-sensitive and hormone-resistant prostate cancer. We further outline potential future incorporation of RT as an immune-sensitizing therapy and the importance of highly sensitive imaging modalities in considering RT in metastatic disease.
Topics: Hormones; Humans; Male; Neoplasm Metastasis; Prostatic Neoplasms; Radiosurgery
PubMed: 35878715
DOI: 10.1016/j.ijrobp.2022.07.014 -
The British Journal of Radiology Mar 2022
Topics: Artificial Intelligence; Humans; Magnetic Resonance Imaging; Male; Multiparametric Magnetic Resonance Imaging; Neoplasm Staging; Prostatic Neoplasms
PubMed: 35179398
DOI: 10.1259/bjr.20229003 -
The Urologic Clinics of North America Aug 2021Recent studies show that the prevalence of germline pathogenic and likely pathogenic variants (also known as mutations) in DNA repair genes in metastatic prostate cancer... (Review)
Review
Recent studies show that the prevalence of germline pathogenic and likely pathogenic variants (also known as mutations) in DNA repair genes in metastatic prostate cancer is higher than previously recognized and higher than in unaffected men. Specific gene dysfunction is important in prostate cancer initiation and/or evolution to metastases. This article reviews key literature on individual genes, recognizing BRCA2 as the gene most commonly altered in the metastatic setting. This article discusses the importance of representative and diverse inclusion, and efforts to advance management for at-risk carrier populations to maximize clinical benefit.
Topics: Antineoplastic Agents; DNA Damage; Genetic Predisposition to Disease; Genetic Testing; Germ-Line Mutation; Humans; Indoles; Male; Neoplasm Metastasis; Phthalazines; Piperazines; Prostatic Neoplasms
PubMed: 34210490
DOI: 10.1016/j.ucl.2021.03.005