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https://www.readbyqxmd.com/read/29761524/the-24th-annual-prostate-cancer-foundation-scientific-retreat-report
#1
REVIEW
Andrea K Miyahira, Howard R Soule
INTRODUCTION: The 24th Annual Prostate Cancer Foundation (PCF) Scientific Retreat was held from October 5-7, 2017, at the Omni Shoreham Hotel in Washington, DC. METHODS: The PCF Scientific Retreat is a scientific conference that specifically focuses on cutting edge research deemed to have significant promise for accelerating advances in prostate cancer biology and treatment. RESULTS: Themes highlighted at this year's meeting included: (i) new understandings in prostate cancer biology and disease progression; (ii) new mechanisms and treatment targets in advanced prostate cancer; (iii) advances in precision medicine genomics, germline genetics, and selection of targeted therapies; (iv) PSMA-targeted agents for PET imaging and radionuclide therapy; (v) approaches for improving the efficacy of immunotherapy in prostate cancer; (vi) applications of 3D Genomics in prostate cancer research; and (vii) potential applications of artificial intelligence in prostate cancer...
May 15, 2018: Prostate
https://www.readbyqxmd.com/read/29752021/hyperthermic-treatment-at-56-%C3%A2-c-induces-tumour-specific-immune-protection-in-a-mouse-model-of-prostate-cancer-in-both-prophylactic-and-therapeutic-immunization-regimens
#2
Francesco De Sanctis, Sara Sandri, Matteo Martini, Marta Mazzocco, Alessandra Fiore, Rosalinda Trovato, Stefano Garetto, Davide Brusa, Stefano Ugel, Silvia Sartoris
Most active cancer immunotherapies able to induce a long-lasting protection against tumours are based on the activation of tumour-specific cytotoxic T lymphocytes (CTLs). Cell death by hyperthermia induces apoptosis followed by secondary necrosis, with the production of factors named "danger associated molecular pattern" (DAMP) molecules (DAMPs), that activate dendritic cells (DCs) to perform antigen uptake, processing and presentation, followed by CTLs cross priming. In many published studies, hyperthermia treatment of tumour cells is performed at 42-45 °C; these temperatures mainly promote cell surface expression of DAMPs...
May 8, 2018: Vaccine
https://www.readbyqxmd.com/read/29734647/recent-advances-in-prostate-cancer-treatment-and-drug-discovery
#3
REVIEW
Ekaterina Nevedomskaya, Simon J Baumgart, Bernard Haendler
Novel drugs, drug sequences and combinations have improved the outcome of prostate cancer in recent years. The latest approvals include abiraterone acetate, enzalutamide and apalutamide which target androgen receptor (AR) signaling, radium-223 dichloride for reduction of bone metastases, sipuleucel-T immunotherapy and taxane-based chemotherapy. Adding abiraterone acetate to androgen deprivation therapy (ADT) in order to achieve complete androgen blockade has proven highly beneficial for treatment of locally advanced prostate cancer and metastatic hormone-sensitive prostate cancer (mHSPC)...
May 4, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29709495/morphological-changes-induced-by-intraprostatic-psa-based-vaccine-in-prostate-cancer-biopsies-phase-i-clinical-trial
#4
Maria J Merino, A Peter, Vanessa Moreno, Sara Gil, Jeffrey Schlom, James L Gulley
Immunotherapy is a novel treatment for many tumors including prostate cancer. Little is known about the histological changes in prostate biopsies caused by the prostatic-specific antigen (PSA)-based vaccine. This study evaluated the histopathological effects in prostate biopsies of recombinant fowlpox (rF) virus-based vaccine engineered to present the PSA and three costimulatory molecules (collectively labeled as PSA-TRICOM). This vaccine has shown that it can break tolerance of the PSA, and its administration directly into a tumor enables the affected tumor cells to act as antigen-presenting cells activating new T-cells, and broadening the immune response to recognize and kill tumor...
April 27, 2018: Human Pathology
https://www.readbyqxmd.com/read/29693186/combined-inhibition-of-jak1-2-stat3%C3%A2-pd%C3%A2-l1-signaling-pathway-suppresses-the-immune-escape-of-castration%C3%A2-resistant-prostate-cancer-to-nk-cells-in-hypoxia
#5
Li-Jun Xu, Qi Ma, Jin Zhu, Jian Li, Bo-Xin Xue, Jie Gao, Chuan-Yang Sun, Ya-Chen Zang, Yi-Bin Zhou, Dong-Rong Yang, Yu-Xi Shan
Castration‑resistant prostate cancer (CRPC) is difficult to treat in current clinical practice. Hypoxia is an important feature of the CRPC microenvironment and is closely associated with the progress of CRPC invasion. However, no research has been performed on the immune escape of CRPC from NK cells. The present study focused on this subject. Firstly, when the CRPC cell lines C4‑2 and CWR22Rv1 were induced by hypoxia, the expression of the UL16 binding protein (ULBP) ligand family of natural killer (NK) group 2D (NKG2D; ULBP‑1, ULBP‑2 and ULBP‑3) and MHC class I chain‑related proteins A and B (MICA/MICB) decreased...
April 20, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29686284/multi-faceted-immunomodulatory-and-tissue-tropic-clinical-bacterial-isolate-potentiates-prostate-cancer-immunotherapy
#6
Jonathan F Anker, Anum F Naseem, Hanlin Mok, Anthony J Schaeffer, Sarki A Abdulkadir, Praveen Thumbikat
Immune checkpoint inhibitors have not been effective for immunologically "cold" tumors, such as prostate cancer, which contain scarce tumor infiltrating lymphocytes. We hypothesized that select tissue-specific and immunostimulatory bacteria can potentiate these immunotherapies. Here we show that a patient-derived prostate-specific microbe, CP1, in combination with anti-PD-1 immunotherapy, increases survival and decreases tumor burden in orthotopic MYC- and PTEN-mutant prostate cancer models. CP1 administered intra-urethrally specifically homes to and colonizes tumors without causing any systemic toxicities...
April 23, 2018: Nature Communications
https://www.readbyqxmd.com/read/29686080/systemic-surfaceome-profiling-identifies-target-antigens-for-immune-based-therapy-in-subtypes-of-advanced-prostate-cancer
#7
John K Lee, Nathanael J Bangayan, Timothy Chai, Bryan A Smith, Tiffany E Pariva, Sangwon Yun, Ajay Vashisht, Qingfu Zhang, Jung Wook Park, Eva Corey, Jiaoti Huang, Thomas G Graeber, James Wohlschlegel, Owen N Witte
Prostate cancer is a heterogeneous disease composed of divergent molecular and histologic subtypes, including prostate adenocarcinoma (PrAd) and neuroendocrine prostate cancer (NEPC). While PrAd is the major histology in prostate cancer, NEPC can evolve from PrAd as a mechanism of treatment resistance that involves a transition from an epithelial to a neurosecretory cancer phenotype. Cell surface markers are often associated with specific cell lineages and differentiation states in normal development and cancer...
April 23, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29673712/update-on-systemic-prostate-cancer-therapies-management-of-metastatic-castration-resistant-prostate-cancer-in-the-era-of-precision-oncology
#8
REVIEW
Philipp Nuhn, Johann S De Bono, Karim Fizazi, Stephen J Freedland, Maurizio Grilli, Philip W Kantoff, Guru Sonpavde, Cora N Sternberg, Srinivasan Yegnasubramanian, Emmanuel S Antonarakis
CONTEXT: Introduction of novel agents for the management of advanced prostate cancer provides a range of treatment options with notable benefits for men with metastatic castration-resistant prostate cancer (mCRPC). At the same time, understanding of optimal patient selection, effective sequential use, and development of resistance patterns remains incomplete. OBJECTIVE: To review current systemic therapies and recent advances in drug development for mCRPC and strategies to aid in patient selection and optimal sequencing...
April 16, 2018: European Urology
https://www.readbyqxmd.com/read/29665853/microsatellite-instability-in-prostate-cancer-by-pcr-or-next-generation-sequencing
#9
Jennifer A Hempelmann, Christina M Lockwood, Eric Q Konnick, Michael T Schweizer, Emmanuel S Antonarakis, Tamara L Lotan, Bruce Montgomery, Peter S Nelson, Nola Klemfuss, Stephen J Salipante, Colin C Pritchard
BACKGROUND: Microsatellite instability (MSI) is now being used as a sole biomarker to guide immunotherapy treatment for men with advanced prostate cancer. Yet current molecular diagnostic tests for MSI have not been evaluated for use in prostate cancer. METHODS: We evaluated two next-generation sequencing (NGS) MSI-detection methods, MSIplus (18 markers) and MSI by Large Panel NGS (> 60 markers), and compared the performance of each NGS method to the most widely used 5-marker MSI-PCR detection system...
April 17, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29644451/emerging-therapies-in-metastatic-prostate-cancer
#10
REVIEW
Daniel W Sonnenburg, Alicia K Morgans
PURPOSE OF REVIEW: In the last decade, there have been multiple landmark therapeutic advances for the treatment of metastatic prostate cancer, both in the castration-resistant and hormone-sensitive setting. In this review, we highlight recent progress and ongoing trials for metastatic prostate cancer, including advances in chemotherapy, androgen receptor-directed therapy, targeted therapies, and immunotherapy. RECENT FINDINGS: Several landmark studies for men with metastatic hormone-sensitive prostate cancer demonstrated improvement in overall survival with the addition of docetaxel chemotherapy or abiraterone acetate to standard androgen deprivation therapy...
April 11, 2018: Current Oncology Reports
https://www.readbyqxmd.com/read/29621897/current-and-potential-targets-for-drug-design-in-the-androgen-receptor-pathway-for-prostate-cancer
#11
Achuta Kumar Guddati
Modulating the androgen axis by different agents has been one of the most successful therapeutic interventions in the field of prostate cancer therapy. Newer agents such as abiraterone and enzalutamide have been widely adapted and have contributed to an increase in the overall survival of prostate cancer patients. However, most of these patients will develop resistance to these agents and will need chemotherapy. Areas covered: In this review, this author discusses current agents which modulate the androgen axis, the mechanisms of resistance to these agents and investigative agents which are designed to bypass these mechanisms of resistance...
April 6, 2018: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/29582792/perspectives-on-the-clinical-development-of-immunotherapy-in-prostate-cancer
#12
Lisa M Cordes, James L Gulley, Ravi A Madan
Despite impressive survival benefits with immunotherapy in patients with various solid tumors, the full potential of these agents in prostate cancer has yet to be realized. Sipuleucel-T demonstrated a survival benefit in this population, indicating that prostate cancer is an immunoresponsive disease; however, these results have not been matched by other agents. A large trial with ipilimumab in prostate cancer failed to meet its primary objective, and small trials with PD-1/PD-L1 inhibitors did not yield a significant improvement in overall response...
March 27, 2018: Asian Journal of Andrology
https://www.readbyqxmd.com/read/29569115/-systemic-immune-checkpoint-inhibition-a-promising-treatment-for-urological-tumors
#13
REVIEW
F C Roos, C Becker, M B Stope, I Tsaur
Improved understanding of the immunomodulatory interactions between tumor cells and immune cells has led to new and promising systemic therapeutic approaches in the first- and second-line therapy of urological tumors. Particularly in the case of urothelial carcinoma, for the first time in 20 years, checkpoint inhibitors (PD-1 and PDL-1 inhibitors) provide well-tolerated therapy that achieves response rates of >20% that can be sustained over the long term. This review explains the approach of immunotherapy and summarizes the current phase III clinical situation on urothelial carcinoma and renal cell carcinoma...
March 22, 2018: Der Urologe. Ausg. A
https://www.readbyqxmd.com/read/29554212/combined-immunotherapy-encompassing-intratumoral-poly-iclc-dendritic-cell-vaccination-and-radiotherapy-in-advanced-cancer-patients
#14
M E Rodríguez-Ruiz, J L Perez-Gracia, I Rodríguez, C Alfaro, C Oñate, G Pérez, I Gil-Bazo, A Benito, S Inogés, A López-Diaz de Cerio, M Ponz-Sarvise, L Resano, P Berraondo, B Barbés, S Martin-Algarra, A Gúrpide, M F Sanmamed, C de Andrea, A M Salazar, I Melero
BACKGROUND: Combination immunotherapy has the potential to achieve additive or synergistic effects. Combined local injections of dsRNA analogues (mimicking viral RNA) and repeated vaccinations with tumor-lysate loaded dendritic cells shows efficacy against colon cancer mouse models. In the context of immunotherapy, radiotherapy can exert beneficial abscopal effects. PATIENTS AND METHODS: In this two-cohort pilot phase I study, 15 advanced cancer patients received two 4-week cycles of four intradermal daily doses of monocyte-derived dendritic cells preloaded with autologous tumor lysate and matured for 24h with poly-ICLC (Hiltonol), TNF-α and IFN-α...
March 14, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29553949/recent-advances-in-the-management-of-metastatic-prostate-cancer-optimizing-use-of-existing-therapies-while-searching-for-novel-interventions
#15
Theodore Gourdin
PURPOSE OF REVIEW: Summarizes recent advances in the treatment of metastatic castration-sensitive and castration-resistant prostate cancer. RECENT FINDINGS: New randomized data suggest a survival advantage to early abiraterone in castration-sensitive metastatic prostate cancer. Prospective and retrospective studies are examining sequencing of existing cytotoxic and androgen-receptor-targeted therapies in both castration-sensitive and castration-resistant disease...
May 2018: Current Opinion in Oncology
https://www.readbyqxmd.com/read/29553053/bone-targeted-therapies-to-reduce-skeletal-morbidity-in-prostate-cancer
#16
Tanya B Dorff, Neeraj Agarwal
Bone metastases are the main driver of morbidity and mortality in advanced prostate cancer. Targeting the bone microenvironment, a key player in the pathogenesis of bone metastasis, has become one of the mainstays of therapy in men with advanced prostate cancer. This review will evaluate the data supporting the use of bone-targeted therapy, including (1) bisphosphonates such as zoledronic acid, which directly target osteoclasts, (2) denosumab, a receptor activator of nuclear factor-kappa B (RANK) ligand inhibitor, which targets a key component of bone stromal interaction, and (3) radium-223, an alpha-emitting calcium mimetic, which hones to the metabolically active areas of osteoblastic metastasis and induces double-strand breaks in the DNA...
March 16, 2018: Asian Journal of Andrology
https://www.readbyqxmd.com/read/29548065/immunotherapy-for-prostate-cancer-where-do-we-go-from-here-part-1-prostate-cancer-vaccines
#17
Amar Patel, Lawrence Fong
Immunotherapies have emerged as a revolutionary modality for cancer treatment, and a variety of immune-based approaches are currently being investigated in the field of prostate cancer. Despite the 2010 approval of sipuleucel-T, subsequent progress in prostate cancer immunotherapy development has been limited by disappointing results with novel vaccination approaches and by prostate cancer's general resistance to immune checkpoint blockade. Nevertheless, there remains strong preclinical and clinical evidence to suggest that prostate cancer is a susceptible target for immune therapies...
March 15, 2018: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/29528821/lynch-syndrome-genomics-update-and-imaging-review
#18
Veronica L Cox, Anas A Saeed Bamashmos, Wai Chin Foo, Shiva Gupta, Sireesha Yedururi, Naveen Garg, Hyunseon Christine Kang
Lynch syndrome is the most common hereditary cancer syndrome, the most common cause of heritable colorectal cancer, and the only known heritable cause of endometrial cancer. Other cancers associated with Lynch syndrome include cancers of the ovary, stomach, urothelial tract, and small bowel, and less frequently, cancers of the brain, biliary tract, pancreas, and prostate. The oncogenic tendency of Lynch syndrome stems from a set of genomic alterations of mismatch repair proteins. Defunct mismatch repair proteins cause unusually high instability of regions of the genome called microsatellites...
March 2018: Radiographics: a Review Publication of the Radiological Society of North America, Inc
https://www.readbyqxmd.com/read/29523597/cross-talk-between-myeloid-derived-suppressor-cells-and-mast-cells-mediates-tumor-specific-immunosuppression-in-prostate-cancer
#19
Mario P Colombo, Elena Jachetti, Valeria Cancila, Alice Rigoni, Lucia Bongiovanni, Barbara Cappetti, Beatrice Belmonte, Claudia Enriquez, Patrizia Casalini, Paola Ostano, Barbara Frossi, Sabina Sangaletti, Claudia Chiodoni, Giovanna Chiorino, Carlo E Pucillo, Claudio Tripodo
Immunotherapy, including the use of checkpoint inhibitors, is a potent therapeutic approach for some cancers, but has limited success with prostate tumors, in which immune suppression is instigated by the tumor. The immunosuppressive capacity of mast cells, which promote adenocarcinoma development in the prostate, prompted our investigation on whether mast cells promote tolerance to SV40 Large-T antigen, the transforming oncogene in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice. The incidence of adenocarcinoma was reduced in the offspring of a cross between TRAMP mice and mast cell-deficient KitWsh mice...
March 9, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29520448/targeting-the-tumor-microenvironment-with-immunotherapy-for-genitourinary-malignancies
#20
REVIEW
Ariel E Marciscano, Ravi A Madan
Bacillus Calmette-Guérin in urothelial carcinoma, high-dose interleukin-2 in renal cell carcinoma, and sipuleucel-T in prostate cancer serve as enduring examples that the host immune response can be harnessed to promote effective anti-tumor immunity in genitourinary malignancies. Recently, cancer immunotherapy with immune checkpoint inhibitors has transformed the prognostic landscape leading to durable responses in a subset of urothelial carcinoma and renal cell carcinoma patients with traditionally poor prognosis...
March 8, 2018: Current Treatment Options in Oncology
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