Tumor heterogeneity in muscle-invasive bladder cancer

Kang, Ho Won; Kim, Wun-Jae; Choi, Woonyoung; Yun, Seok Joong

doi:10.21037/tau.2020.03.13

Cited by 11 publications

(7 citation statements)

References 108 publications

(155 reference statements)

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“…There are new proposals of panels and groups of biomarkers to identify bladder cancer subtypes, with state-of-the-art technology. Kang et al, 2020 also illustrate the taxonomic classifications, with suggested treatments for different MIBC subtypes based on molecular biomarkers [109]. The combination of neoadjuvant therapy with immune checkpoint inhibitors (designed for suitable biomarker expression) is currently being tested and is expected to increase efficacy in treatments [110].…”

Section: Bladder Cancer Therapiesmentioning

confidence: 99%

The Role of Androgens and Androgen Receptor in Human Bladder Cancer

et al. 2021

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Bladder cancer (urothelial carcinoma) is one of the most frequently diagnosed neoplasms, with an estimated half a million new cases and 200,000 deaths per year worldwide. This pathology mainly affects men. Men have a higher risk (4:1) of developing bladder cancer than women. Cigarette smoking and exposure to chemicals such as aromatic amines, and aniline dyes have been established as risk factors for bladder cancer and may contribute to the sex disparity. Male internal genitalia, including the urothelium and prostate, are derived from urothelial sinus endoderm; both tissues express the androgen receptor (AR). Several investigations have shown evidence that the AR plays an important role in the initiation and development of different types of cancer including bladder cancer. In this article, we summarize the available data that help to explain the role of the AR in the development and progression of bladder cancer, as well as the therapies used for its treatment.

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Section: Bladder Cancer Therapiesmentioning

confidence: 99%

The Role of Androgens and Androgen Receptor in Human Bladder Cancer

et al. 2021

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“…However, this is not the case with biopsy samples. Here, the ability of Jacalin to distinguish between normal, Ta and T1 tumours is undetectable, presumably due to the differences between patients and within the tumour (Kang et al 2020). Furthermore, T24 and RT4 cells differ from NPU cells in that they bind signi cantly less DSA.…”

Section: Discussionmentioning

confidence: 95%

Selective targeting of lectins and their macropinocytosis in urothelial tumours: translation from in vitro to ex vivo

Resnik

Višnjar

Smrkolj

et al. 2022

Preprint

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Urinary bladder cancer can be treated by intravesical application of therapeutic agents, but the specific targeting of cancer urothelial cells and the endocytotic pathways of the agents are not known. During carcinogenesis, the superficial urothelial cells exhibit changes in sugar residues on the apical plasma membranes. This can be exploited for selective targeting from the luminal side of the bladder. Here we show that the plant lectins Jacalin (from Artocarpus integrifolia), ACA (from Amaranthus caudatus) and DSA (from Datura stramonium) selectively bind to the apical plasma membrane of low-grade (RT4) and high-grade (T24) cancer urothelial cells in vitro and urothelial tumours ex vivo. The amount of lectin binding was significantly different between RT4 and T24 cells. Endocytosis of lectins was observed only in cancer urothelial cells and not in normal urothelial cells. Transmission electron microscopy analysis showed macropinosomes, endosome-like vesicles and multivesicular bodies filled with lectins in RT4 and T24 cells and also in cells of urothelial tumours ex vivo. Endocytosis of Jacalin and ACA in cancer cells was decreased in vitro after addition of inhibitor of macropinocytosis 5-(N-ethyl-N-isopropyl) amiloride (EIPA) and increased after stimulation of macropinocytosis with epidermal growth factor (EGF). Clathrin, caveolin and flotillin did not colocalise with lectins. These results confirm that the predominant mechanism of lectin endocytosis in cancer urothelial cells is macropinocytosis. Therefore, we propose that lectins in combination with conjugated therapeutic agents are promising tools for improved intravesical therapy by targeting cancer cells.

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“…The recurrent nature of bladder tumors, the availability of matched transurethral resection and cystectomy specimens, exfoliated urothelial cells, and the ease of assaying free-circulating DNA, transcripts, and soluble proteins/metabolites in urine have all enabled such investigations. These studies have certainly advanced knowledge about the biology of bladder tumors, but their goal has been the promise of personalized medicine; specifically, molecular tests to predict outcome and response to intravesical, neoadjuvant and adjuvant/salvage treatments and to guide targeted treatment selection [ 7 , 20 , 28 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 ].…”

Section: Molecular Basis Of Bc and Clinical Translationmentioning

confidence: 99%

Molecular Oncology of Bladder Cancer from Inception to Modern Perspective

Lokeshwar

López

Sarcan

et al. 2022

Cancers

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Within the last forty years, seminal contributions have been made in the areas of bladder cancer (BC) biology, driver genes, molecular profiling, biomarkers, and therapeutic targets for improving personalized patient care. This overview includes seminal discoveries and advances in the molecular oncology of BC. Starting with the concept of divergent molecular pathways for the development of low- and high-grade bladder tumors, field cancerization versus clonality of bladder tumors, cancer driver genes/mutations, genetic polymorphisms, and bacillus Calmette-Guérin (BCG) as an early form of immunotherapy are some of the conceptual contributions towards improving patient care. Although beginning with a promise of predicting prognosis and individualizing treatments, “-omic” approaches and molecular subtypes have revealed the importance of BC stem cells, lineage plasticity, and intra-tumor heterogeneity as the next frontiers for realizing individualized patient care. Along with urine as the optimal non-invasive liquid biopsy, BC is at the forefront of the biomarker field. If the goal is to reduce the number of cystoscopies but not to replace them for monitoring recurrence and asymptomatic microscopic hematuria, a BC marker may reach clinical acceptance. As advances in the molecular oncology of BC continue, the next twenty-five years should significantly advance personalized care for BC patients.

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Tumor heterogeneity in muscle-invasive bladder cancer

Cited by 11 publications

References 108 publications

The Role of Androgens and Androgen Receptor in Human Bladder Cancer

The Role of Androgens and Androgen Receptor in Human Bladder Cancer

Selective targeting of lectins and their macropinocytosis in urothelial tumours: translation from in vitro to ex vivo

Molecular Oncology of Bladder Cancer from Inception to Modern Perspective

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