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Targeted therapies for bladder cancer

Kambiz Rahbar, Ali Afshar-Oromieh, Martin Bögemann, Stefan Wagner, Michael Schäfers, Lars Stegger, Matthias Weckesser
PURPOSE: PSMA-targeted PET in patients with prostate cancer (PCa) has a significant impact on treatment decisions. By far the most frequently used PSMA ligand is68 Ga-labelled PSMA-11. However, due to the availability of larger amounts of activity,18 F-labelled PSMA ligands are of major interest. The aim of the present study was to evaluate the biodistribution and performance of the novel18 F-labelled ligand PSMA-1007 at two different time points. METHODS: This retrospective analysis included 40 consecutive patients (mean age 68...
March 14, 2018: European Journal of Nuclear Medicine and Molecular Imaging
Taro Funakoshi, Takahiro Horimatsu, Michio Nakamura, Koichi Shiroshita, Koichi Suyama, Masashi Mukoyama, Takuro Mizukami, Tsutomu Sakurada, Eishi Baba, Kazuhiko Tsuruya, Akira Nozaki, Kensei Yahata, Yukinori Ozaki, Yoshifumi Ubara, Hisateru Yasui, Akihiro Yoshimoto, Shingo Fukuma, Naoya Kondo, Takeshi Matsubara, Kazuo Matsubara, Shunichi Fukuhara, Motoko Yanagita, Manabu Muto
Background: Cancer is a major cause of death in patients undergoing haemodialysis. However, information about the actual clinical practice of chemotherapy for patients with cancer undergoing haemodialysis is lacking. We conducted a nationwide survey using questionnaires on the clinical practice of chemotherapy for such patients. Patients and methods: The nationwide survey included patients undergoing haemodialysis who were subsequently diagnosed with cancer in 20 hospitals in Japan from January 2010 to December 2012...
2018: ESMO Open
Rita Azevedo, Janine Soares, Andreia Peixoto, Sofia Cotton, Luís Lima, Lúcio Lara Santos, José Alexandre Ferreira
CONTEXT: Circulating tumor cells (CTC) in peripheral blood of cancer patients provide an opportunity for real-time liquid biopsies capable of aiding early intervention, therapeutic decision, response to therapy, and prognostication. Nevertheless, the rare and potentially heterogeneous molecular nature of CTC has delayed the standardization of robust high-throughput capture/enrichment and characterization technologies. OBJECTIVE: This review aims to systematize emerging solutions for CTC analysis in bladder cancer (BC), their opportunities and limitations, while providing key insights on specific technologic aspects that may ultimately guide molecular studies and clinical implementation...
March 9, 2018: Urologic Oncology
Hiroki Nagai, Manabu Muto
Over the last two decades, molecular-targeted agents have become mainstream treatment for many types of malignancies and have improved the overall survival of patients. However, most patients eventually develop resistance to these targeted therapies. Recently, immunotherapies such as immune checkpoint inhibitors have revolutionized the treatment paradigm for many types of malignancies. Immune checkpoint inhibitors have been approved for treatment of melanoma, non-small cell lung cancer, renal cell carcinoma, head and neck squamous cell carcinoma, Hodgkin's lymphoma, bladder cancer and gastric cancer...
March 7, 2018: International Journal of Clinical Oncology
Freddy E Escorcia, Jeffrey M Steckler, Dalya Abdel-Atti, Eric W Price, Sean D Carlin, Wolfgang W Scholz, Jason S Lewis, Jacob L Houghton
PURPOSE: Tumor-specific molecular imaging is an important tool for assessing disease burden and treatment response. CA19.9 is an important tumor-specific marker in several malignancies, including urothelial carcinoma. [89 Zr]DFO-HuMab-5B1 (MVT-2163) is a CA19.9-specific antibody-based construct that has been validated in preclinical animal models of lung, colorectal, and pancreatic malignancies for positron emission tomography (PET) imaging and is currently in a phase I trial for pancreatic cancer (NCT02687230)...
March 5, 2018: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
Haibiao Xie, Hengji Zhan, Qunjun Gao, Jianfa Li, Qun Zhou, Zhicong Chen, Yuhan Liu, Mengting Ding, Huizhong Xiao, Yuchen Liu, Weiren Huang, Zhiming Cai
Both oncogenic transcription factors (TFs) and microRNAs (miRNAs) play important roles in human cancers, acting as transcriptional and post-transcriptional regulators, respectively. These phenomena raise questions about the ability of an artificial device to simultaneously regulate miRNAs and TFs. In this study, we aimed to construct artificial long non-coding RNAs, "alncRNAs", and to investigate their therapeutic effects on bladder cancer cell lines. Based on engineering principles of synthetic biology, we combined tandem arrayed aptamer cDNA sequences for TFs with tandem arrayed cDNA copies of binding sites for the miRNAs to construct alncRNAs...
March 1, 2018: Cancer Letters
Vijaya Sarangthem, Eun A Cho, Aena Yi, Sang Kyoon Kim, Byung-Heon Lee, Rang-Woon Park
Expression of various molecules on the surface of cancer cells compared to normal cells creates a platform for the generation of various drug vehicles for targeted therapy. Multiple interactions between ligands and their receptors mediated by targeting peptide-modified polymer could enable simultaneous delivery of a drug selectively to target tumor cells, thus limiting side effects resulting from non-specific drug delivery. In this study, we synthesized a novel tumor targeting system by using two key elements: (1) Bld-1 peptide (SNRDARRC), a recently reported bladder tumor targeting peptide identified by using a phage-displayed peptide library, and (2) ELP, a thermally responsive polypeptide...
March 1, 2018: Scientific Reports
Jane Dobson, Genilson Fernandes de Queiroz, Jon P Golding
Photodynamic therapy (PDT) is an evolving method of treating superficial tumours that is non-invasive and carries minimal risk of toxicity. It combines tumour-selective photosensitiser dyes, tissue oxygen and targeted illumination to generate cytotoxic reactive oxygen species (ROS) within the tumour. In addition to directly acting on tumour cells, PDT damages and restricts tumour microvasculature, and causes a local inflammatory response that stimulates an immune response against the tumour. Unlike surgery or radiotherapy, the surrounding extracellular matrix is unaffected by PDT; thus, tissue healing is excellent and PDT seldom causes scars...
March 2018: Veterinary Journal
Mingfang Guo, Erliang Huang, Xianfeng Liu, Ying Tang
BACKGROUND: The aim of this study was to compare the dosimetric parameters, clinical complications, and efficacy of volumetric modulated arc therapy (VMAT) and fixed-field intensity-modulated radiotherapy (f-IMRT) in radical radiotherapy for cervical cancer without lymphadenectasis. METHODS: 84 cervical cancer patients undergoing treatment with VMAT and f-IMRT were selected. Dose-volume histograms were used to evaluate the dose distribution in the planning target volume (PTV) and organs at risk...
2018: Oncology Research and Treatment
Michael L Cheng, Gopa Iyer
A sea change has occurred in the treatment options available for metastatic urothelial bladder cancer with the recent Food and Drug Administration approval of 5 immune checkpoint blockade agents for patients who have progressed on platinum-based chemotherapy or are not candidates for cisplatin. Additionally, comprehensive characterization of the landscape of genomic alterations in this disease through The Cancer Genome Atlas and other efforts has detected numerous potential targets for small molecule inhibitors...
February 19, 2018: Urologic Oncology
Hiroyuki Okamoto, Naoya Murakami, C Claudia Carvajal, Yuki Miura, Akihisa Wakita, Satoshi Nakamura, Shie Nishioka, Kotaro Iijima, Koji Inaba, Yoshinori Ito, Tomoyasu Kato, Takafumi Toita, Jun Itami
PURPOSE: To propose a geometrical margin for definition of the vaginal cuff PTV using only CT images of the full bladder (CTfull ) in postoperative cervical cancer patients. METHODS: Twenty-nine operated cervical cancer patients underwent volumetric arc therapy with a bladder filling protocol. This study assessed bladder filling using a portable bladder scanner and cone-beam computed tomography (CBCT) during the entire treatment period. The measured bladder volumes with a BladderScan® were compared with the delineated volume on CBCT...
January 2018: Physica Medica: PM
Lena Thomas, Steffi Kantz, Arthur Hung, Debra Monaco, Florian C Gaertner, Markus Essler, Holger Strunk, Wolfram Laub, Ralph A Bundschuh
PURPOSE: The purpose of our study was to show the feasibility and potential benefits of using68 Ga-PSMA-PET/CT imaging for radiation therapy treatment planning of patients with primary prostate cancer using either integrated boost on the PET-positive volume or localized treatment of the PET-positive volume. The potential gain of such an approach, the improvement of tumor control, and reduction of the dose to organs-at-risk at the same time was analyzed using the QUANTEC biological model...
February 21, 2018: European Journal of Nuclear Medicine and Molecular Imaging
Tingsheng Lin, Xiaozhi Zhao, Sheng Zhao, Hang Yu, Wenmin Cao, Wei Chen, Hui Wei, Hongqian Guo
Photodynamic therapy (PDT) is an emerging effective treatment for cancer. However, the great promise of PDT for bladder cancer therapy has not yet been realized because of tumor hypoxia. To address this challenge, we fabricated O2 -generating HSA-MnO2 -Ce6 NPs (HSA for human serum albumin, Ce6 for chlorin e6, and NPs for nanoparticles) to overcome tumor hypoxia and thus enhance the photodynamic effect for bladder cancer therapy. Methods: The HSA-MnO2 -Ce6 NPs were prepared. We investigated the O2 generation of NPs in vitro and in vivo ...
2018: Theranostics
Mélanie Mahe, Florent Dufour, Hélène Neyret-Kahn, Aura Moreno-Vega, Claire Beraud, Mingjun Shi, Imene Hamaidi, Virginia Sanchez-Quiles, Clementine Krucker, Marion Dorland-Galliot, Elodie Chapeaublanc, Remy Nicolle, Hervé Lang, Celio Pouponnot, Thierry Massfelder, François Radvanyi, Isabelle Bernard-Pierrot
FGFR3 alterations (mutations or translocation) are among the most frequent genetic events in bladder carcinoma. They lead to an aberrant activation of FGFR3 signaling, conferring an oncogenic dependence, which we studied here. We discovered a positive feedback loop, in which the activation of p38 and AKT downstream from the altered FGFR3 upregulates MYC mRNA levels and stabilizes MYC protein, respectively, leading to the accumulation of MYC, which directly upregulates FGFR3 expression by binding to active enhancers upstream from FGFR3 Disruption of this FGFR3/MYC loop in bladder cancer cell lines by treatment with FGFR3, p38, AKT, or BET bromodomain inhibitors (JQ1) preventing MYC transcription decreased cell viability in vitro and tumor growth in vivo A relevance of this loop to human bladder tumors was supported by the positive correlation between FGFR3 and MYC levels in tumors bearing FGFR3 mutations, and the decrease in FGFR3 and MYC levels following anti-FGFR treatment in a PDX model bearing an FGFR3 mutation...
February 20, 2018: EMBO Molecular Medicine
Donika Plyku, Esther Mena, Steven P Rowe, Martin A Lodge, Zsolt Szabo, Steve Y Cho, Martin G Pomper, George Sgouros, Robert F Hobbs
PURPOSE: Prostate-specific membrane antigen (PSMA), a type-II integral membrane protein highly expressed in prostate cancer, has been extensively used as a target for imaging and therapy. Among the available PET radiotracers, the low molecular weight agents that bind to PSMA are proving particularly effective. We present the dosimetry results for18 F-DCFPyL in nine patients with metastatic prostate cancer. METHODS: Nine patients were imaged using sequential PET/CT scans at approximately 1, 12, 35 and 70 min, and a final PET/CT scan at approximately 120 min after intravenous administration of 321 ± 8 MBq (8...
February 19, 2018: European Journal of Nuclear Medicine and Molecular Imaging
Thomas Sanford, Maxwell V Meng, Reema Railkar, Piyush K Agarwal, Sima P Porten
Background: Elucidation of epigenetic alterations in bladder cancer will lead to further understanding of the biology of the disease and hopefully improved therapies. Our aim was to perform an integrative epigenetic analysis of invasive urothelial carcinoma of the bladder to identify the epigenetic abnormalities involved in the development and progression of this cancer. Methods: Pre-processed methylation data and RNA-seq data were downloaded from The Cancer Genome Atlas (TCGA) and processed using the R package TCGA-Assembler...
2018: Clinical Epigenetics
Marina Pulido, Guilhem Roubaud, Anne-Laure Cazeau, Hakim Mahammedi, Lionel Vedrine, Florence Joly, Loic Mourey, Christian Pfister, Alejandro Goberna, Barbara Lortal, Carine Bellera, Philippe Pourquier, Nadine Houédé
BACKGROUND: Bladder cancer is the 7th cause of death from cancer in men and 10th in women. Metastatic patients have a poor prognosis with a median overall survival of 14 months. Until recently, vinflunine was the only second-line chemotherapy available for patients who relapse. Deregulation of the PI3K/AKT/mTOR pathway was observed in more than 40% of bladder tumors and suggested the use of mTOR as a target for the treatment of urothelial cancers. METHODS: This trial assessed the efficacy of temsirolimus in a homogenous cohort of patients with recurrent or metastatic bladder cancer following first-line chemotherapy...
February 17, 2018: BMC Cancer
Sounak Gupta, Divya Sahu, John S Bomalaski, Igor Frank, Stephen A Boorjian, Prabin Thapa, John C Cheville, Donna E Hansel
High-grade neuroendocrine carcinomas (HGNECs) of the urinary bladder encompass small cell (SCNEC) and large cell neuroendocrine carcinomas (LCNEC). Currently, recommended initial management is with systemic chemotherapy, followed by consolidative therapy with either radical cystectomy or radiotherapy in patients with localized disease. Nevertheless, survival in this setting remains poor. We therefore evaluated the potential to modify arginine metabolism as an alternative, targeted therapy approach in these carcinomas...
February 16, 2018: Endocrine Pathology
Pushpak Bhandari, Gloriia Novikova, Craig J Goergen, Joseph Irudayaraj
New intravesical treatment approaches for bladder cancer are needed as currently approved treatments show several side effects and high tumor recurrence rate. Our study used MB49 murine urothelial carcinoma model to evaluate oxygen encapsulated cellulosic nanobubbles as a novel agent for imaging and ultrasound guided drug delivery. In this study, we show that oxygen nanobubbles (ONB) can be propelled (up to 40 mm/s) and precisely guided in vivo to the tumor by an ultrasound beam. Nanobubble velocity can be controlled by altering the power of the ultrasound Doppler beam, while nanobubble direction can be adjusted to different desired angles by altering the angle of the beam...
February 15, 2018: Scientific Reports
Lee Goddard, Nils P Brodin, William R Bodner, Madhur Garg, Wolfgang A Tomé
OBJECTIVE: To investigate whether photon or proton based SBRT is the preferred modality for high dose hypofractionation prostate cancer treatment. Achievable dose distributions were compared when uncertainties in target positioning and range uncertainties were appropriately accounted for. METHODS: Ten patients with prostate cancer previously treated at our institution with photon SBRT using volumetric modulated arc therapy (VMAT) were identified. MRI images fused to the treatment planning CT allowed for accurate target and organ-at-risk (OAR) delineation...
February 13, 2018: British Journal of Radiology
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