Addressing the need for more therapeutic options in neuroendocrine prostate cancer

INTRODUCTION Neuroendocrine Prostate Cancer (NEPC) is an aggressive form of prostate cancer frequently seen after prolonged treatment of Castration Resistant Prostate Cancer (CRPC). NEPC has become increasingly prevalent over the last 20 years, with a poor prognosis caused by a late diagnosis and limited treatment options. Recent advances in PET/CT imaging and targeted radioimmunotherapy are promising, but more research into additional treatment options is needed. AREAS COVERED The aim of this review is to analyze the current imaging and treatment options for NEPC, and to highlight future potential treatment strategies. A Pubmed search for "Neuroendocrine Prostate Cancer" was performed and relevant articles were reviewed. EXPERT OPINION The recent FDA approval and success of 177 PSMA Lutetium in CRPC is promising, as 177 Lutetium could potentially be paired with a NEPC specific biomarker for targeted therapy. Recent laboratory studies pairing DLL3, which is overexpressed in NEPC, with 177 Lutetium and new PET agents have showed good efficacy in identifying and treating NEPC. The success of future development of NEPC therapies may depend on the availability of 177 Lutetium, as current supplies are limited. Further research into additional imaging and treatment options for NEPC is warranted.

[1]  C. Rudin,et al.  Delta-like ligand 3–targeted radioimmunotherapy for neuroendocrine prostate cancer , 2022, Proceedings of the National Academy of Sciences of the United States of America.

[2]  Joel Vargas Ahumada,et al.  Multitarget Molecular Imaging in Metastatic Castration Resistant Adenocarcinoma Prostate Cancer with Therapy Induced Neuroendocrine Differentiation , 2022, Diagnostics.

[3]  M. Oya,et al.  Multiple metastases of androgen indifferent prostate cancer in the urinary tract: two case reports and a literature review , 2022, BMC medical genomics.

[4]  Tanya Stoyanova,et al.  Molecular Mechanisms Underlying the Development of Neuroendocrine Prostate Cancer. , 2022, Seminars in cancer biology.

[5]  J. Wisco,et al.  Novel forms of prostate cancer chemoresistance to successful androgen deprivation therapy demand new approaches: Rationale for targeting BET proteins , 2022, The Prostate.

[6]  D. Vriens,et al.  Clinical Pharmacology of Radiotheranostics in Oncology , 2022, Clinical pharmacology and therapeutics.

[7]  T. Tomás,et al.  Male Breast Metastasis: A Case of Treatment-Emergent Neuroendocrine Prostate Cancer , 2022, Cureus.

[8]  Amritha Sreekumar,et al.  Role of MicroRNAs in Neuroendocrine Prostate Cancer , 2022, Non-coding RNA.

[9]  H. Yaegashi,et al.  Treatment Outcomes in Neuroendocrine Prostate Cancer , 2022, AntiCancer Research.

[10]  M. Harrison,et al.  A phase 2 trial of avelumab in men with aggressive-variant or neuroendocrine prostate cancer , 2022, Prostate Cancer and Prostatic Diseases.

[11]  Feng Zhang,et al.  miR-145-5p Inhibits Neuroendocrine Differentiation and Tumor Growth by Regulating the SOX11/MYCN Axis in Prostate cancer , 2022, Frontiers in Genetics.

[12]  Changhong Shi,et al.  Monoamine oxidase A drives neuroendocrine differentiation in prostate cancer , 2022, Biochemical and Biophysical Research Communications.

[13]  F. Ban,et al.  Development of VPC-70619, a Small-Molecule N-Myc Inhibitor as a Potential Therapy for Neuroendocrine Prostate Cancer , 2022, International journal of molecular sciences.

[14]  G. Shao,et al.  68Ga-DOTA-NT-20.3 Neurotensin Receptor 1 PET Imaging as a Surrogate for Neuroendocrine Differentiation of Prostate Cancer , 2022, The Journal of Nuclear Medicine.

[15]  K. Pantel,et al.  Aggressive variants of prostate cancer: underlying mechanisms of neuroendocrine transdifferentiation , 2022, Journal of Experimental & Clinical Cancer Research.

[16]  Yanting Shen,et al.  Reprogramming hormone-sensitive prostate cancer to a lethal neuroendocrine cancer lineage by mitochondrial pyruvate carrier (MPC) , 2022, Molecular metabolism.

[17]  G. Raj,et al.  The central role of Sphingosine kinase 1 in the development of neuroendocrine prostate cancer (NEPC): A new targeted therapy of NEPC , 2022, Clinical and translational medicine.

[18]  C. Rudin,et al.  Molecular Imaging of Neuroendocrine Prostate Cancer by Targeting Delta-Like Ligand 3 , 2022, The Journal of Nuclear Medicine.

[19]  R. Ummanni,et al.  Activation of TGF-β - SMAD2 signaling by IL-6 drives neuroendocrine differentiation of prostate cancer through p38MAPK. , 2022, Cellular signalling.

[20]  Jen C Wang,et al.  Review of Checkpoint Inhibitor Immunotherapy in Neuroendocrine Tumor of Prostate and Our Experience in 2 Cases , 2022, Journal of investigative medicine high impact case reports.

[21]  P. Vlachostergios,et al.  Expression of Fibroblast Activation Protein Is Enriched in Neuroendocrine Prostate Cancer and Predicts Worse Survival , 2022, Genes.

[22]  Antonio Yaromin Muñoz López,et al.  Primary neuroendocrine prostate cancer with adrenal gland metastasis , 2021, Urology case reports.

[23]  Chien-Chin Chen,et al.  The Crosstalk of Long Non-Coding RNA and MicroRNA in Castration-Resistant and Neuroendocrine Prostate Cancer: Their Interaction and Clinical Importance , 2021, International journal of molecular sciences.

[24]  M. Oya,et al.  First successful case of platinum‐based chemotherapy for neuroendocrine prostate cancer with BRCA2 and PTEN alterations , 2021, IJU Case Reports.

[25]  Jun Luo,et al.  Reciprocal YAP1 loss and INSM1 expression in neuroendocrine prostate cancer , 2021, The Journal of pathology.

[26]  R. Karnes,et al.  Expression of ISL1 and its partners in prostate cancer progression and neuroendocrine differentiation , 2021, Journal of Cancer Research and Clinical Oncology.

[27]  B. Bensing,et al.  Novel, non-invasive markers for detecting therapy induced neuroendocrine differentiation in castration-resistant prostate cancer patients , 2021, Scientific Reports.

[28]  K. Kitajima,et al.  Pelvic MRI, FDG-PET/CT, and Somatostatin Receptor Scintigraphy Findings of Treatment-Related Neuroendocrine-Differentiated Prostate Cancer , 2021, Case Reports in Oncology.

[29]  S. Morbelli,et al.  Neuroendocrine Differentiation of Prostate Cancer Is Not Systematically Associated with Increased 18F-FDG Uptake , 2021, Diagnostics.

[30]  T. Akhurst,et al.  Molecular Imaging of Neuroendocrine Differentiation of Prostate Cancer: A Case Series. , 2021, Clinical genitourinary cancer.

[31]  X. Qiu,et al.  Treatment-Emergent Neuroendocrine Prostate Cancer: A Clinicopathological and Immunohistochemical Analysis of 94 Cases , 2021, Frontiers in Oncology.

[32]  Henry W. Long,et al.  Reprogramming of the FOXA1 cistrome in treatment-emergent neuroendocrine prostate cancer , 2020, Nature Communications.

[33]  J. Qin,et al.  Histone demethylase PHF8 drives neuroendocrine prostate cancer progression by epigenetically upregulating FOXA2 , 2020, The Journal of pathology.

[34]  T. Özülker,et al.  Assessment of the role of Ga-68 PSMA I&T PET/CT in response evaluation to docetaxel therapy in castration resistant prostate cancer patients , 2020, Revista Española de Medicina Nuclear e Imagen Molecular (English Edition).

[35]  O. Dirsch,et al.  Evaluation of Somatostatin and CXCR4 Receptor Expression in a Large Set of Prostate Cancer Samples Using Tissue Microarrays and Well-Characterized Monoclonal Antibodies , 2020, Translational oncology.

[36]  M. Benešová,et al.  [68Ga]Ga-DOTA-TOC: The First FDA-Approved 68Ga-Radiopharmaceutical for PET Imaging , 2020, Pharmaceuticals.

[37]  H. G. van der Poel,et al.  Use of gallium‐68 prostate‐specific membrane antigen positron‐emission tomography for detecting lymph node metastases in primary and recurrent prostate cancer and location of recurrence after radical prostatectomy: an overview of the current literature , 2019, BJU international.

[38]  O. Elemento,et al.  Clinical features of neuroendocrine prostate cancer. , 2019, European journal of cancer.

[39]  Satya N. Das,et al.  177Lu-DOTATATE for the treatment of gastroenteropancreatic neuroendocrine tumors , 2019, Expert review of gastroenterology & hepatology.

[40]  V. Khoo,et al.  Prostate‐specific membrane antigen‐positron emission tomography/computed tomography (PSMA‐PET/CT)‐guided stereotactic ablative body radiotherapy for oligometastatic prostate cancer: a single‐institution experience and review of the published literature , 2019, BJU international.

[41]  Yuzhuo Wang,et al.  Treatment-emergent neuroendocrine prostate cancer: molecularly driven clinical guidelines , 2019, International Journal of Endocrine Oncology.

[42]  Yigang Zhao,et al.  Comparison of PSMA-PET/CT, choline-PET/CT, NaF-PET/CT, MRI, and bone scintigraphy in the diagnosis of bone metastases in patients with prostate cancer: a systematic review and meta-analysis , 2019, Skeletal Radiology.

[43]  Yi Mi Wu,et al.  Genomic correlates of clinical outcome in advanced prostate cancer , 2019, Proceedings of the National Academy of Sciences.

[44]  Kevin P. Banks,et al.  Review of 18F-Fluciclovine PET for Detection of Recurrent Prostate Cancer. , 2019, Radiographics : a review publication of the Radiological Society of North America, Inc.

[45]  O. Elemento,et al.  Delta-like protein 3 expression and therapeutic targeting in neuroendocrine prostate cancer , 2019, Science Translational Medicine.

[46]  Chawnshang Chang,et al.  Neurotensin and its receptors mediate neuroendocrine transdifferentiation in prostate cancer , 2019, Oncogene.

[47]  T. Graeber,et al.  Systemic surfaceome profiling identifies target antigens for immune-based therapy in subtypes of advanced prostate cancer , 2018, Proceedings of the National Academy of Sciences.

[48]  K. Rahbar,et al.  External radiation exposure, excretion, and effective half-life in 177Lu-PSMA-targeted therapies , 2018, EJNMMI Research.

[49]  V. Lowe,et al.  Prostate cancer-specific PET radiotracers: A review on the clinical utility in recurrent disease. , 2018, Practical radiation oncology.

[50]  M. Schwaiger,et al.  Preliminary results on response assessment using 68Ga-HBED-CC-PSMA PET/CT in patients with metastatic prostate cancer undergoing docetaxel chemotherapy , 2018, European Journal of Nuclear Medicine and Molecular Imaging.

[51]  F. Montorsi,et al.  Contemporary Incidence and Cancer Control Outcomes of Primary Neuroendocrine Prostate Cancer: A SEER Database Analysis , 2017, Clinical genitourinary cancer.

[52]  Kathy Willowson,et al.  Lutetium 177 PSMA radionuclide therapy for men with prostate cancer: a review of the current literature and discussion of practical aspects of therapy , 2017, Journal of medical radiation sciences.

[53]  K. Pienta,et al.  Correlation of PSMA-Targeted 18F-DCFPyL PET/CT Findings With Immunohistochemical and Genomic Data in a Patient With Metastatic Neuroendocrine Prostate Cancer. , 2017, Clinical genitourinary cancer.

[54]  J. Bono,et al.  Radiographic progression with nonrising PSA in metastatic castration-resistant prostate cancer: post hoc analysis of PREVAIL , 2017, Prostate Cancer and Prostatic Diseases.

[55]  Henry W. Long,et al.  Rb1 and Trp53 cooperate to suppress prostate cancer lineage plasticity, metastasis, and antiandrogen resistance , 2017, Science.

[56]  Joshua M. Stuart,et al.  N-Myc Drives Neuroendocrine Prostate Cancer Initiated from Human Prostate Epithelial Cells. , 2016, Cancer cell.

[57]  Matteo Benelli,et al.  Divergent clonal evolution of castration resistant neuroendocrine prostate cancer , 2016, Nature Medicine.

[58]  S. Paulson,et al.  Neuroendocrine Carcinoma of the Prostate Gland , 2016, Proceedings.

[59]  K. Nikolaou,et al.  Comparison of 68Ga-labelled PSMA-11 and 11C-choline in the detection of prostate cancer metastases by PET/CT , 2016, European Journal of Nuclear Medicine and Molecular Imaging.

[60]  S. Fanti,et al.  Prospective Comparison of 18F-Fluoromethylcholine Versus 68Ga-PSMA PET/CT in Prostate Cancer Patients Who Have Rising PSA After Curative Treatment and Are Being Considered for Targeted Therapy , 2015, The Journal of Nuclear Medicine.

[61]  Zhaoqin Huang,et al.  Use of 11C-Choline positron emission tomography/computed tomography to investigate the mechanism of choline metabolism in lung cancer , 2015, Molecular medicine reports.

[62]  S. Fanti,et al.  11C-Choline PET/CT in castration-resistant prostate cancer patients treated with docetaxel , 2015, European Journal of Nuclear Medicine and Molecular Imaging.

[63]  T. Holland-Letz,et al.  The diagnostic value of PET/CT imaging with the 68Ga-labelled PSMA ligand HBED-CC in the diagnosis of recurrent prostate cancer , 2014, European Journal of Nuclear Medicine and Molecular Imaging.

[64]  M. Zelefsky,et al.  Utility of FDG‐PET in clinical neuroendocrine prostate cancer , 2014, The Prostate.

[65]  G. Sauter,et al.  Loss of Somatostatin Receptor Subtype 2 in Prostate Cancer Is Linked to an Aggressive Cancer Phenotype, High Tumor Cell Proliferation and Predicts Early Metastatic and Biochemical Relapse , 2014, PloS one.

[66]  G. Savelli,et al.  Neuroendocrine Differentiation of Prostate Cancer Metastases Evidenced “in Vivo” by 68Ga-DOTANOC PET/CT: Two Cases , 2014, World journal of oncology.

[67]  J. Epstein,et al.  Small cell carcinoma of the prostate , 2014, Nature Reviews Urology.

[68]  Adam T Froemming,et al.  Detection of Recurrent Prostate Cancer After Radical Prostatectomy: Comparison of 11C-Choline PET/CT with Pelvic Multiparametric MR Imaging with Endorectal Coil , 2014, The Journal of Nuclear Medicine.

[69]  J. Reubi,et al.  Illuminating somatostatin analog action at neuroendocrine tumor receptors. , 2013, Trends in pharmacological sciences.

[70]  A. Osunkoya,et al.  A comprehensive review of incidence and survival in patients with rare histological variants of prostate cancer in the United States from 1973 to 2008 , 2012, Prostate Cancer and Prostatic Diseases.

[71]  S. Culine,et al.  Phase II study of carboplatin and etoposide in patients with anaplastic progressive metastatic castration-resistant prostate cancer (mCRPC) with or without neuroendocrine differentiation: results of the French Genito-Urinary Tumor Group (GETUG) P01 trial. , 2011, Annals of oncology : official journal of the European Society for Medical Oncology.

[72]  D. Tindall,et al.  Androgen receptor signaling in prostate cancer development and progression , 2011, Journal of carcinogenesis.

[73]  Lily Wu,et al.  Comprehensive evaluation of the role of EZH2 in the growth, invasion, and aggression of a panel of prostate cancer cell lines , 2010, The Prostate.

[74]  V. Ambrosini,et al.  Is there a role for 11C-choline PET/CT in the early detection of metastatic disease in surgically treated prostate cancer patients with a mild PSA increase <1.5 ng/ml? , 2010, European Journal of Nuclear Medicine and Molecular Imaging.

[75]  B. Krause,et al.  68Ga-DOTATOC-PET/CT detects neuroendocrine differentiation of prostate cancer metastases , 2009, Nuklearmedizin.

[76]  P. di Sant'Agnese,et al.  Immunohistochemical characterization of neuroendocrine cells in prostate cancer , 2006, The Prostate.

[77]  J. Reubi Peptide receptors as molecular targets for cancer diagnosis and therapy. , 2003, Endocrine reviews.

[78]  J. Shimazaki,et al.  Progression of prostate cancer to neuroendocrine cell tumor , 2001, International journal of urology : official journal of the Japanese Urological Association.