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Targeted therapies for bladder cancer

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https://www.readbyqxmd.com/read/29160225/phosphatidylserine-targeted-single-walled-carbon-nanotubes-for-photothermal-ablation-of-bladder-cancer
#1
Needa A Virani, Carole Davis, Patrick McKernan, Paul Hauser, Robert E Hurst, Joel Slaton, Ricardo P Silvy, Daniel E Resasco, Roger G Harrison
Bladder cancer has a 60-70% recurrence rate most likely due to residual tumour left behind after a transurethral resection (TUR). Failure to completely resect the cancer can lead to recurrence and progression into higher grade tumours with metastatic potential. We present here a novel therapy to treat superficial tumours with the potential to decrease recurrence. The therapy is a heat-based approach in which bladder tumour specific single-walled carbon nanotubes (SWCNTs) are delivered intravesically at a very low dose (0...
November 21, 2017: Nanotechnology
https://www.readbyqxmd.com/read/29157296/biomarkers-for-immunotherapy-in-bladder-cancer-a-moving-target
#2
REVIEW
David H Aggen, Charles G Drake
Treatment options for metastatic urothelial carcinoma (mUC) remained relative unchanged over the last 30 years with combination chemotherapy as the mainstay of treatment. Within the last year the landscape for mUC has seismically shifted following the approval of five therapies targeting the programmed cell death protein (PD-1)/programmed cell death ligand 1 (PD-L1) axis. Notably, the anti-PD-1 antibody pembrolizumab demonstrated improved OS relative to chemotherapy in a randomized phase III study for second line treatment of mUC; this level 1 evidence led to approval from the U...
November 21, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29154981/egfr-family-inhibition-identifies-p38-mapk-as-a-potential-therapeutic-target-in-bladder-cancer
#3
Regina Mora Vidal, Sergio Regufe da Mota, Annette Hayden, Hannah Markham, James Douglas, Graham Packham, Simon J Crabb
Objective To investigate perturbations in downstream signalling pathway activation and potential resistance mechanisms to EGFR and/or HER2 inhibition in cell line models of bladder cancer. Methods We undertook a structured screening approach by phosphokinase array, followed by validation steps, to detect activated downstream signalling pathway nodes after therapeutic inhibition of EGFR and/or HER2 in bladder cancer cell lines. Results Erlotinib treatment of RT112 cells induced phosphorylation of 9 activated phospho-protein targets (p38 MAPK (Thr180/Tyr182), GSK-3α/β (Ser21/9), MEK1/2 (Ser218/222, Ser222/226), Akt (Ser473), TOR (Ser2448), Src (Tyr419), p27 (Thr198), p27 (Thr157) and PLCγ-1 (Tyr783)) whereas STAT4 (Tyr693) phosphorylation was reduced...
November 15, 2017: Urology
https://www.readbyqxmd.com/read/29147616/mrna-expression-levels-of-genes-involved-in-antitumor-immunity-identification-of-a-3-gene-signature-associated-with-prognosis-of-muscle-invasive-bladder-cancer
#4
Constance Le Goux, Sophie Vacher, Géraldine Pignot, Mathilde Sibony, Nicolas Barry Delongchamps, Benoit Terris, Eliane Piaggio, Marc Zerbib, Diane Damotte, Ivan Bieche
Immunotherapy for bladder cancer has given promising results. Here we aimed to evaluate the possible involvement and prognostic value of 33 genes involved in the immune response during bladder carcinogenesis. Expression levels were assessed by quantitative real-time RT-PCR in normal and tumor human bladder samples. Immunohistochemistry was performed to evaluate the protein expression of 2 genes and relation of the mRNA and protein levels was analyzed. Tumors were obtained from 154 patients (83 with muscle-invasive bladder cancer [MIBC] and 71 non-MIBC [NMIBC]) who underwent transurethral bladder resection or radical cystectomy between 2002 and 2006...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29133939/precision-medicine-for-urothelial-bladder-cancer-update-on-tumour-genomics-and-immunotherapy
#5
REVIEW
Kenneth M Felsenstein, Dan Theodorescu
Effective management of advanced urothelial bladder cancer is challenging. New discoveries that improve our understanding of molecular bladder cancer subtypes have revealed numerous potentially targetable genomic alterations and demonstrated the efficacy of treatments that harness the immune system. These findings have begun to change paradigms of bladder cancer therapy. For example, DNA repair pathway mutations in genes such as ERCC2, FANCC, ATM, RB1, and others can predict responses to neoadjuvant platinum-based chemotherapies and to targeted therapies on the basis of mutation status...
November 14, 2017: Nature Reviews. Urology
https://www.readbyqxmd.com/read/29125888/circular-rna-hsa_circ_0003221-circptk2-promotes-the-proliferation-and-migration-of-bladder-cancer-cells
#6
Zhen-Qiang Xu, Ming-Gen Yang, Hong-Jie Liu, Chen-Qiang Su
Emerging studies have shown that circular RNAs could be ideal biomarkers and even potential therapeutic targets for some tumors, including bladder cancer. However, only a few studies have investigated the circular RNAs in human bladder cancer. The key circular RNA molecules are closely related to bladder cancer and their roles remain largely unknown. Here, we investigated a novel circular RNA molecule, hsa-circ-0003221(circPTK2), which is differentially expressed in bladder carcinoma. Significant differential expression levels of circPTK2 were confirmed with quantitative PCR in 40 pairs of tissue and blood samples from patients with bladder carcinoma...
November 10, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29123949/targeting-il-5r%C3%AE-with-antibody-conjugates-reveals-a-strategy-for-imaging-and-therapy-for-invasive-bladder-cancer
#7
Michel Paquette, Luis-Guillermo Vilera-Perez, Simon Beaudoin, Nadia Ekindi-Ndongo, Pierre-Luc Boudreaut, Marc-Andre Bonin, Marie-Claude Battista, M'hamed Bentourkia, Angel F Lopez, Roger Lecomte, Eric Marsault, Brigitte Guérin, Robert Sabbagh, Jeffrey V Leyton
Despite the high interest and concern due to an increasing incidence and death rate, patients who develop muscle invasive bladder cancer (MIBC) have few options available. However, the past decade has produced many candidate bladder tumor-specific markers but further development of these markers is still needed for creating effective targeted medications to solve this urgent need. Interleukin-5 receptor α-subunit (IL-5Rα) has recently been reported to be involved in MIBC progression. Thus, we aimed to validate IL-5Rα as a target for antibody-conjugates to better manage patients with MIBC...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29121415/efficacy-and-safety-of-trametinib-in-japanese-patients-with-advanced-biliary-tract-cancers-refractory-to-gemcitabine
#8
Masafumi Ikeda, Tatsuya Ioka, Akira Fukutomi, Chigusa Morizane, Akiyoshi Kasuga, Hideaki Takahashi, Akiko Todaka, Takuji Okusaka, Caretha L Creasy, Shelby Gorman, Daniel J Felitsky, Mikiro Kobayashi, Fanghong Zhang, Junji Furuse
Gemcitabine-based therapy remains the mainstay of treatment for patients with biliary tract cancers (BTCs) with no second-line treatment(s) established yet. Aberrant activation of MAPK pathway in patients with BTC indicates its importance in BTC. Trametinib is a potent, highly selective, allosteric non-competitive inhibitor of MEK1/MEK2. In this Phase IIa open-label, single-arm study, we investigated efficacy and safety of trametinib in Japanese patients with advanced BTC refractory to gemcitabine-based therapy...
November 9, 2017: Cancer Science
https://www.readbyqxmd.com/read/29101415/target-tailoring-and-proton-beam-therapy-to-reduce-small-bowel-dose-in-cervical-cancer-radiotherapy-a-comparison-of-benefits
#9
Peter de Boer, Agustinus J A J van de Schoot, Henrike Westerveld, Mark Smit, Marrije R Buist, Arjan Bel, Coen R N Rasch, Lukas J A Stalpers
PURPOSE: The aim of the study was to investigate the potential clinical benefit from both target tailoring by excluding the tumour-free proximal part of the uterus during image-guided adaptive radiotherapy (IGART) and improved dose conformity based on intensity-modulated proton therapy (IMPT). METHODS: The study included planning CTs from 11 previously treated patients with cervical cancer with a >4-cm tumour-free part of the proximal uterus on diagnostic magnetic resonance imaging (MRI)...
November 3, 2017: Strahlentherapie und Onkologie: Organ der Deutschen Röntgengesellschaft ... [et Al]
https://www.readbyqxmd.com/read/29077785/impact-of-contemporary-patterns-of-chemotherapy-utilization-on-survival-in-patients-with-advanced-cancer-of-the-urinary-tract-a-retrospective-international-study-of-invasive-advanced-cancer-of-the-urothelium-risc
#10
A Bamias, K Tzannis, L C Harshman, S J Crabb, Y-N Wong, S Kumar Pal, U De Giorgi, S Ladoire, N Agarwal, E Y Yu, G Niegisch, A Necchi, C N Sternberg, S Srinivas, A Alva, U Vaishampayan, L Cerbone, M Liontos, J Rosenberg, T Powles, J Belmunt, M D Galsky
BackgroundCisplatin-based combination chemotherapy is the standard treatment for advanced urinary tract cancer (aUTC) but 50% of patients are ineligible for cisplatin according to recently published criteria. We used a multinational database to study patterns of chemotherapy utilization in patients with aUTC and determine their impact on survival.Patients and MethodsThis was a retrospective study of patients with: UTC (bladder, renal pelvis, ureter or urethra); advanced disease (stages T4b and/or N+ and/or M+); urothelial, squamous or adenocarcinoma histology...
October 25, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29069302/mechanistic-overview-of-immune-checkpoints-to-support-the-rational-design-of-their-combinations-in-cancer-immunotherapy
#11
A Rotte, J Y Jin, V Lemaire
Checkpoint receptor blockers, known to act by blocking the pathways that inhibit immune cell activation and stimulate immune responses against tumor cells, have been immensely successful in the treatment of cancer. Among several checkpoint receptors of immune cells, cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), programmed cell death protein-1 (PD-1), T-cell immunoglobulin and ITIM domain (TIGIT), T-cell immunoglobulin-3 (TIM-3) and lymphocyte activation gene 3 (LAG-3) are the most commonly targeted checkpoints for cancer immunotherapy...
October 24, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29048677/microrna-154-as-a-prognostic-factor-in-bladder-cancer-inhibits-cellular-malignancy-by-targeting-rsf1-and-runx2
#12
Xin Zhao, Zhigang Ji, Yi Xie, Guanghua Liu, Hanzhong Li
Recent studies have demonstrated that microRNA-154 (miR-154) is involved in tumorigenesis, progression, invasion and metastasis in several types of human cancer. However, whether it plays a role in bladder cancer (BC) is unclear. The aim of the present study was to determine miR-154 levels in human BC tissues and investigate the correlation between miR-154 levels and clinicopathological characteristics as well as patient outcome. Using RT-qPCR, we found that the expression levels of miR-154 were significantly lower in BC tissues compared to adjacent normal tissues...
September 25, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29048631/autophagy-induction-enhances-tetrandrine-induced-apoptosis-via-the-ampk-mtor-pathway-in-human-bladder-cancer-cells
#13
Bo Kou, Wei Liu, Xu Xu, Yang Yang, Qiuyue Yi, Fengwei Guo, Jianpeng Li, Jinsong Zhou, Qingshan Kou
Tetrandrine, a bisbenzylisoquinoline alkaloid isolated from the roots of Stephania tetrandra is a traditional Chinese medicine and exerts anticancer capacity in various types of cancers. Previous studies have shown that tetrandrine induces apoptosis in bladder cancer cells via activation of the caspase cascade. However, the underlying mechanism has not yet been reported. Autophagy is a cellular process involved in the degradation of broken proteins and aging organelles to maintain homeostasis. Recent studies indicate that autophagy is implicated in cancer therapy...
September 21, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29042936/the-expression-of-vasohibin-1-and-its-prognostic-significance-in-bladder-cancer
#14
Bo Zhang, Zhouliang Wu, Wanqin Xie, Dawei Tian, Feiran Chen, Chuan Qin, Zhiyong Du, Gang Tang, Qiongqiong Gao, Xiaoyu Qiu, Changli Wu, Jing Tian, Hailong Hu
Angiogenesis is important in the development of solid tumors. Vasohibin-1 (VASH-1) is an endothelium-derived protein that acts as an inhibitor of angiogenesis in many different types of cancer. However, the expression of VASH-1 and its clinical value in bladder cancer remain unknown. The current study analyzed the expression of VASH-1, as well as the expression of the angiogenesis-related factors vascular endothelial growth factor-A, hypoxia inducible factor-1α and cluster of differentiation 34 in bladder cancer tissues from 50 patients using immunohistochemistry...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29032338/an-analysis-of-suppressing-migratory-effect-on-human-urinary-bladder-cancer-cell-line-by-silencing-of-snail-1
#15
Shima Salehi, Behzad Mansoori, Ali Mohammadi, Sadaf Davoudian, Seyed Mohammad Hossein Musavi Shenas, Neda Shajari, Jafar Majidi, Behzad Baradaran
BACKGROUND: Snail-1 actively participates in tumor progression, invasion, and migration. Targeting snail-1 expression can suppress the EMT process in cancer. The aim of this study was to investigate the effect of snail1 silencing on urinary bladder cancer. METHODS: Quantitative RT-PCR was used to detect snail-1 and other related metastatic genes expression following siRNA knockdown in urinary bladder cancer EJ-138 cells. The protein level of snail1 was assessed by Western blot...
October 12, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29032188/genito-urinary-genomics-and-emerging-biomarkers-for-immunomodulatory-cancer-treatment
#16
REVIEW
Thomas Gevaert, Rodolfo Montironi, Antonio Lopez-Beltran, Geert Van Leenders, Yves Allory, Dirk De Ridder, Frank Claessens, Mark Kockx, Murat Akand, Steven Joniau, George Netto, Louis Libbrecht
Immunotherapy is gradually becoming a key factor in the therapeutic algorithm for patients with genito-urinary (GU) cancers at different stages of disease. Robust and reliable biomarkers are crucial for an appropriate inclusion of patients in clinical trials and for a reliable patient selection for treatments with immunomodulatory drugs. The increasing knowledge on the genomic landscape of GU cancers supports stratification of patients for targeted therapies. This review focusses on emerging biomarkers and the role of genomics in predicting clinical benefit to immunomodulatory agents in GU cancers...
October 12, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29031916/image-guided-adaptive-external-beam-radiation-therapy-for-cervix-cancer-evaluation-of-a-clinically-implemented-plan-of-the-day-technique
#17
Martin Buschmann, Katarina Majercakova, Alina Sturdza, Stephanie Smet, Dina Najjari, Michaela Daniel, Richard Pötter, Dietmar Georg, Yvette Seppenwoolde
BACKGROUND: Radiotherapy for cervix cancer is challenging in patients exhibiting large daily changes in the pelvic anatomy, therefore adaptive treatments (ART) have been proposed. The aim of this study was the clinical implementation and subsequent evaluation of plan-of-the-day (POTD)-ART for cervix cancer in supine positioning. The described workflow was based on standard commercial equipment and current quality assurance (QA) methods. MATERIALS AND METHODS: A POTD strategy, which employs a VMAT plan library consisting of an empty bladder plan, a full bladder plan and a motion robust backup plan, was developed...
October 11, 2017: Zeitschrift Für Medizinische Physik
https://www.readbyqxmd.com/read/29031069/synthesis-and-biological-evaluation-of-a-platinum-ii-c-rgdyk-conjugate-for-integrin-targeted-photodynamic-therapy
#18
T Chatzisideri, S Thysiadis, S Katsamakas, P Dalezis, I Sigala, T Lazarides, E Nikolakaki, D Trafalis, O A Gederaas, M Lindgren, V Sarli
A cancer-targeting conjugate 4 of a cyclometalated [N,C,N-Pt(II)] complex bearing a NˆCˆN 1,3-di(2-pyridyl)-benzene with c(RGDyK) peptide as guiding molecule was designed and synthesized for real-time drug delivery monitoring in cancer cells and photodynamic therapy (PDT). This conjugate demonstrates a mild cytostatic effect to six cancer cell lines expressing integrins at different extent, while possessing promising features for PDT. Conjugate 4 demonstrated rapid cell uptake by receptor-mediated endocytosis and efficient generation of (1)O2 upon irradiation...
December 1, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29025984/synthesis-and-biological-evaluation-of-a-novel-18-f-labeled-adnectin-as-a-pet-radioligand-for-imaging-pd-l1-expression
#19
David J Donnelly, Ralph Adam Smith, Paul Morin, Dasa Lipovsek, Jochem Gokemeijer, Daniel Cohen, Virginie Lafont, Tritin Tran, Erin Lee Cole, Martin Wright, Joonyoung Kim, Adrienne Pena, Daniel Kukral, Douglas D Dischino, Patrick Chow, Jinping Gan, Olufemi Adelakun, Xi-Tao Wang, Kai Cao, David Lueng, Samuel Bonacorsi, Wendy Hayes
The programmed death protein (PD-1) and its ligand (PD-L1) play critical roles in a checkpoint pathway cancer cells exploit to evade the immune system. A same-day PET imaging agent for measuring PD-L1 status in primary and metastatic lesions could be important for optimizing drug therapy. Herein, we have evaluated the tumor targeting of an anti-PD-L1 Adnectin after (18)F-fluorine labeling. Methods: An anti-PD-L1 Adnectin was labeled with (18)F in two steps. This synthesis featured fluorination of a novel prosthetic group, followed by a copper-free click conjugation to a modified Adnectin to generate (18)F-BMS-986192...
October 12, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28994323/atezolizumab-in-invasive-and-metastatic-urothelial-carcinoma
#20
Michael Crist, Arjun Balar
Until recently, there has been little advancement in the management of invasive and metastatic urothelial cancer in over 30 years, and outcomes with cisplatin-based chemotherapy remain unchanged. Inhibitors targeting PD-1 signaling on cytotoxic T-cells have revolutionized bladder cancer therapy leading to durable responses. Atezolizumab is an engineered humanized anti-PD-L1 monoclonal antibody that inhibits PD-L1 binding to PD-1 and B7.1, enhancing immune-mediated tumor killing and is currently approved as second-line treatment after failure of platinum-based chemotherapy as well as first-line in cisplatin-ineligible patients...
October 10, 2017: Expert Review of Clinical Pharmacology
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