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Hope and Challenge: Precision Medicine in Bladder Cancer

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Hope and Challenge: Precision Medicine in Bladder Cancer Received: 6 November 2018 | Revised: 20 December 2018 | Accepted: 1 January 2019 DOI: 10.1002/cam4.1979 REVIEW Hope and challenge: Precision medicine in bladder cancer Hongwei Su1 | Haitao Jiang2,3 | Tao Tao2,4 | Xing Kang2 | Xu Zhang2 | Danyue Kang5 | Shucheng Li2 | Chengxi Li2 | Haifeng Wang6 | Zhao Yang7 | Jinku Zhang8 | Chong Li1,2,4,9 1Department of Urology, Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, China 2Core Facility for Protein Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China 3School of Medical Laboratory Science and Biotechnology, Taipei Medical University, Taipei, China 4Department of Urology, The Affiliated Luohu Hospital of Shenzhen University, Shenzhen University, Shenzhen, China 5Michigan State University, East Lansing, Michigan 6Department of Urology, The Second Affliated Hospital of Kunming Medical University, Kunming, China 7College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China 8Department of pathology, First Central Hospital of Baoding, Baoding, Hebei, China 9Beijing Jianlan Institute of Medicine, Beijing, China Correspondence Chong Li, Core Facility for Protein Abstract Research, Institute of Biophysics, Chinese Bladder cancer (BC) is a complex disease and could be classified into nonmuscle‐in- Academy of Sciences, Beijing, China. vasive BC (NMIBC) or muscle‐invasive BC (MIBC) subtypes according to the dis- Email: [email protected] Zhao Yang, College of Life Science and tinct genetic background and clinical prognosis. Until now, the golden standard and Technology, Beijing University of Chemical confirmed diagnosis of BC is cystoscopy and the major problems of BC are the high Technology, Beijing, China. rate of recurrence and high costs in the clinic. Recent molecular and genetic studies Email: [email protected] and have provided perspectives on the novel biomarkers and potential therapeutic targets Jinku Zhang, Department of pathology, of BC. In this article, we provided an overview of the traditional diagnostic ap- First Central hospital of Baoding, Baoding, proaches of BC, and introduced some new imaging, endoscopic, and immunological Hebei, China. Email: [email protected]. diagnostic technology in the accurate diagnosis of BC. Meanwhile, the minimally invasive precision treatment technique, immunotherapy, chemotherapy, gene ther- Funding Information This work was supported by the National apy, and targeted therapy of BC were also included. Here, we will overview the di- Natural Science Foundation of China agnosis and therapy methods of BC used in clinical practice, focusing on their (81672956, 81472413 to C. Li, 81602644 to Z. Yang, 81660422 to H. Wang), the specificity, efficiency, and safety. On the basis of the discussion of the benefits of National Key Research and Development precision medicine in BC, we will also discuss the challenges and limitations facing Program (2017YFA0105900) and the the non‐invasive methods of diagnosis and precision therapy of BC. The molecularly Beijing Science and Technology Project (Z181100003818003). targeted and immunotherapeutic approaches, and gene therapy methods to BC treat- ment improved the prognosis and overall survival of BC patients. KEYWORDS bladder cancer, gene therapy, immunotherapy, precision medicine These authors contributed equally: Hongwei Su, Haitao Jiang, Tao Tao This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. 1806 | wileyonlinelibrary.com/journal/cam4 Cancer Medicine. 2019;8:1806–1816. SU ET AL. | 1807 1 | INTRODUCTION (NMP22), fibrin/fibrinogen degradation products (FDP), Immunocytochemistry, Fluorescent in situ hybridization Bladder cancer (BC) is a common urinary malignant tumor.1 (FISH), etc.7 Bell et al suggested that the high expression of In 2012, bladder cancer ranks as the ninth most common‐di- NMP22 in urine was related to a decreased recurrence‐free agnosed cancer with estimated 430,000 new cases.1,2 BC is survival and progression‐free survival (PFS) in bladder can- the most prevalent urinary cancer in China, the ratio of the cer concurrently.8 A study of Yafi et al indicated that the incidence BC for males to females and cities to rural areas is combination of urine cytology and NMP22 could effectively 3.3 and 2.4, respectively. For the past few years, the overall improve the rate of early diagnosis of high‐grade tumor.9 incidence and mortality of BC have shown a gradual upward Li et al addressed that AG‐α3β1 (the antigen recognized by trend and become a serious threat to the health of people.1-3 BCMab1) was closely related to the progression and progno- With the development of minimally invasive urology tech- sis of BC, and could be used as a biomarker for early diagno- nique and a new initiative on precision medicine, the treat- sis or postoperative recurrence of BC.10,11 ment of BC enters the epoch of precision medicine. Precision Furthermore, the biomarkers in early diagnosis and post- medicine, also called personalized medicine, is a novel med- operative monitoring of BC include telomerase, hyaluronic ical concept. The cross‐application of genome sequencing, acid (HA), hyaluronidase (HAase), microRNA, long non- proteomics technology, bioinformatics, and big data analysis coding RNA (lncRNA), DNA methylation, survivin, micro- are applied to investigate the etiological factors, precise clas- satellite alteration (MA), cell‐free plasma DNA (cfp‐DNA), sification, and therapeutic targets of disease at the molecular and circulating tumor cell (CTC).12-14 Roperch et al pointed level, ultimately actualize precise personalized medicine, and out DNA methylation combined with the mutation status of improve the prophylactic and therapeutic effect of diseases.4,5 FGFR3 resulted in an accurate diagnosis for NMIBC with a In 2015, former U.S. president Obama lodged “precision specificity and sensitivity of 97.6% and 84.8%, respectively.15 medicine initiative” and intended to make precision medicine Martens‐Uzunova et al emphasized that lncRNA could be concept penetrating into various medical fields. They have in- used as a novel non‐invasive tumor marker for the diagnosis vested a mass of resources in the project to carry out in‐depth of urinary tumor.16 investigations. Therefore, precision medicine is the general trend of medical development.6 2.3 | New imaging technology Imaging techniques are of great consequence in the accu- 2 RESEARCH FRONT OF | rate diagnosis of BC, which include multi‐slice spiral CT, PRECISION DIAGNOSIS IN transurethral ultrasound of bladder, positron emission to- BLADDER CANCER mography/computed tomography (PET/CT), and target im- aging.17-23 FDG PET/CT exhibited a significant prognostic 2.1 Traditional diagnostic approach | value in assessing progression‐free survival and overall Major diagnosis methods of BC are imaging tests (ultra- survival, which was validated in patients with suspected re- sound, CT, MRI), cystoscopy, and urine cytology presently current BC.20 Meta‐analysis showed that PET/CT could ac- (Table 1a). These examinations have high accuracy in pa- curately monitor the metastasis of BC. However, it is difficult tients with advanced BC and biopsy is the gold standard for to assess the primary lesion of BC patients by PET/CT.21 bladder cancer screening. Urine cytology is a non‐invasive pH low insertion peptides (pHLIP, Table 1c), a mem- method. However, it has poor sensitivity and might be influ- brane‐bound peptide, can specifically target acidic cells both enced by factors such as kidney stone, renal inflammation, in vitro and in vivo when cells are in a low pH environment.22 and hemorrhage. Cystoscopy is an invasive technique that The study of Golijanin et al demonstrated that ICG‐pHLIP may miss diagnose small tumors, carcinoma in situ (CIS), targeted imaging could specifically recognize advanced and inflammatory carcinoma. Therefore, finding the precise, urothelial carcinoma (including MIBC and NMIBC) and non‐invasive, painless, economical, and convenient methods improve the early diagnosis of BC, which provided a novel of early diagnosis for BC has become a hotspot in recent alternative for the diagnosis and treatment of BC. years. 2.4 | New endoscopic imaging technique 2.2 Tumor markers in diagnosis of | New endoscopic imaging techniques for the diagnosis of bladder cancer BC mainly include fluorescence cystoscopy, narrow spec- The urinary tumor markers and methods approved trum optical cystoscopy, optical coherence tomography and by FDA were used for BC diagnosis including blad- confocal laser endoscopy, etc. (Table 1d). With the help of der cancer antigen (BTA), nuclear matrix protein 22 photosensitizer, such as 5‐ALA and its derivative HAL, the SU ET AL. 1808 TABLE 1 A summary of modality in the diagnosis of bladder cancer | Method Description Pros Cons Refs (a) Traditional diagnostic approaches Urine cytology Using a microscope to look for cancer cells in This examination is of high accuracy for patients Not finding cancer on this test does not always mean ACS urine with advanced bladder cancer patients are cancer free Ultrasound It uses sound waves to create images of It can be useful in determining the size of a bladder The accuracy is poor when flat, plaque like tumors ACS internal organs cancer and whether it has metastasis are present,
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