Pathobiology and Chemoprevention of Bladder Cancer

Our understanding of the pathogenesis of bladder cancer has improved considerably over the past decade. Translating these novel pathobiological discoveries into therapies, prevention, or strategies to manage patients who are suspected to have or who have been diagnosed with bladder cancer is the ultimate goal. In particular, the chemoprevention of bladder cancer development is important, since urothelial cancer frequently recurs, even if the primary cancer is completely removed. The numerous alterations of both oncogenes and tumor suppressor genes that have been implicated in bladder carcinogenesis represent novel targets for therapy and prevention. In addition, knowledge about these genetic alterations will help provide a better understanding of the biological significance of preneoplastic lesions of bladder cancer. Animal models for investigating bladder cancer development and prevention can also be developed based on these alterations. This paper summarizes the results of recent preclinical and clinical chemoprevention studies and discusses screening for bladder cancer.

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Erdafitinib: A novel therapy for FGFR-mutated urothelial cancer

American Journal of Health-System Pharmacy ◽

10.1093/ajhp/zxz329 ◽

2020 ◽

Vol 77 (5) ◽

pp. 346-351 ◽

Cited By ~ 2

Author(s):

Kiera Roubal ◽

Zin W Myint ◽

Jill M Kolesar

Keyword(s):

Bladder Cancer ◽

Urothelial Cancer ◽

Growth Factor Receptor ◽

Progression Free Survival ◽

Clinical Effectiveness ◽

Genetic Alterations ◽

Novel Therapy ◽

Days Of Therapy ◽

Phase 2 Clinical Trial ◽

Gene Alterations

Abstract Purpose To provide an overview of fibroblast growth factor receptor (FGFR) gene alterations and the pharmacology, clinical effectiveness, dosage and administration, cost, and place in therapy of erdafitinib in bladder cancer. Summary Erdafitinib (Balversa, Janssen Pharmaceuticals) is a novel pan-FGFR inhibitor recently approved for the treatment of patients with advanced urothelial cancer with specific FGFR genetic alterations who have received at least one prior platinum-containing regimen. Erdafitinib binding to the FGFR2 and FGFR3 receptors inhibits FGF activity, resulting in cell death. Erdafitinib is available in tablet form, and the current recommended daily dosing is 8 mg, with dose escalation to 9 mg after 14 to 21 days of therapy if tolerated. A phase 2 clinical trial demonstrated that patients who received erdafitinib experienced on average 5.5 months of progression-free survival (95% confidence interval [CI], 4.2-6.0 months). In addition, 40% (95% CI, 31-50%) of patients responded to erdafitinib therapy. Patients receiving erdafitinib therapy should be monitored specifically for elevations in serum phosphate levels and changes in vision. Other adverse effects include anemia, thrombocytopenia, and electrolyte abnormalities. Conclusion Erdafitinib is the first small-molecule FGFR inhibitor approved for use in advanced bladder cancer.

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Personalized medicine in advanced urothelial cancer: when to treat, how to treat and who to treat

Canadian Urological Association Journal ◽

10.5489/cuaj.1204 ◽

2013 ◽

Vol 3 (6-S4) ◽

pp. 232 ◽

Cited By ~ 3

Author(s):

Behfar Ehdaie ◽

Steven C. Smith ◽

Dan Theodorescu

Keyword(s):

Bladder Cancer ◽

Urothelial Cancer ◽

Systematic Approach ◽

Cancer Diagnostics ◽

The Past ◽

Tumorigenesis And Progression ◽

Metastatic Urothelial Carcinoma ◽

Advanced Urothelial Cancer ◽

Patient Prognosis ◽

Representative Cohort

The past decade has provided an improved understanding of themolecular mechanism of bladder cancer by defining distinct pathwaysin tumorigenesis and progression. Advances in technologies,such as high-throughput transcript profiling, microarrays andproteomics, offer a systematic approach to identifying targets forbladder cancer diagnostics and drug discovery. This review presentsa select outline of the advances in the development of biomarkersand targets for patient prognosis and therapy selection.This paper describes a representative cohort of recent studies thathave the potential to significantly impact the management of muscleinvasive and metastatic urothelial carcinoma of the bladder.Space constraints do not permit this review to be comprehensiveand we apologize to the authors whose work we do not cite.

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Therapeutic Advances in Oncology

International Journal of Molecular Sciences ◽

10.3390/ijms22042008 ◽

2021 ◽

Vol 22 (4) ◽

pp. 2008

Author(s):

Jinsha Liu ◽

Priyanka Pandya ◽

Sepideh Afshar

Keyword(s):

Small Molecules ◽

New Technologies ◽

Treatment Options ◽

Current Treatment ◽

Bispecific Antibodies ◽

Gene Therapies ◽

Therapeutic Modalities ◽

The Past ◽

Drug Conjugates ◽

Novel Targets

Around 77 new oncology drugs were approved by the FDA in the past five years; however, most cancers remain untreated. Small molecules and antibodies are dominant therapeutic modalities in oncology. Antibody-drug conjugates, bispecific antibodies, peptides, cell, and gene-therapies are emerging to address the unmet patient need. Advancement in the discovery and development platforms, identification of novel targets, and emergence of new technologies have greatly expanded the treatment options for patients. Here, we provide an overview of various therapeutic modalities and the current treatment options in oncology, and an in-depth discussion of the therapeutics in the preclinical stage for the treatment of breast cancer, lung cancer, and multiple myeloma.

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Sex Hormone Receptor Signaling in Bladder Cancer: A Potential Target for Enhancing the Efficacy of Conventional Non-Surgical Therapy

Cells ◽

10.3390/cells10051169 ◽

2021 ◽

Vol 10 (5) ◽

pp. 1169

Author(s):

Hiroki Ide ◽

Hiroshi Miyamoto

Keyword(s):

Bladder Cancer ◽

Estrogen Receptor ◽

Androgen Receptor ◽

Surgical Therapy ◽

Urothelial Cancer ◽

Hormone Receptors ◽

Estrogen Receptor Α ◽

Vital Role ◽

Sex Hormone ◽

Sex Steroid Hormone

There have been critical problems in the non-surgical treatment for bladder cancer, especially residence to intravesical pharmacotherapy, including BCG immunotherapy, cisplatin-based chemotherapy, and radiotherapy. Recent preclinical and clinical evidence has suggested a vital role of sex steroid hormone-mediated signaling in the progression of urothelial cancer. Moreover, activation of the androgen receptor and estrogen receptor pathways has been implicated in modulating sensitivity to conventional non-surgical therapy for bladder cancer. This may indicate the possibility of anti-androgenic and anti-estrogenic drugs, apart from their direct anti-tumor activity, to function as sensitizers of such conventional treatment. This article summarizes available data suggesting the involvement of sex hormone receptors, such as androgen receptor, estrogen receptor-α, and estrogen receptor-β, in the progression of urothelial cancer, focusing on their modulation for the efficacy of conventional therapy, and discusses their potential of overcoming therapeutic resistance.

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Cell cycle arrest and astrocytic differentiation resulting from PTEN expression in glioma cells

Journal of Neurosurgery ◽

10.3171/jns.1999.91.5.0822 ◽

1999 ◽

Vol 91 (5) ◽

pp. 822-830 ◽

Cited By ~ 33

Author(s):

Jun-ichi Adachi ◽

Katsumi Ohbayashi ◽

Tomonari Suzuki ◽

Tomio Sasaki

Keyword(s):

Expression System ◽

Biological Significance ◽

Glioma Cells ◽

Genetic Alterations ◽

Pten Expression ◽

Human Glioma ◽

Wild Type ◽

Content Type ◽

Astrocytic Differentiation ◽

Fine Print

Object. Genetic alterations of the PTEN gene (also known as MMAC1 or TEP1) have frequently been identified in high-grade gliomas, indicating that inactivation of PTEN plays a crucial role in human glioma progression. The aim of this study was to assess the biological significance of PTEN inactivation in the development of glioma.Methods. The authors introduced wild-type PTEN complementary DNA into four human glioma cell lines (T98G, U-251MG, U-87MG, and A172) containing endogenous aberrant PTEN alleles. The number of colonies transfected with the wild-type PTEN was reduced to 15 to 32% of those found after transfection of a control vector, suggesting growth suppression by the exogenous PTEN. To analyze phenotypic alterations produced by PTEN expression, T98G-derived clones with inducible PTEN expression were further established using a tetracycline-regulated inducible gene expression system. Induction of PTEN expression suppressed the in vitro growth of T98G cells with accumulation of G1 phase cells. Furthermore, when cells were cultured in the presence of the extracellular matrix (ECM), PTEN expression caused distinct morphological changes, with multiple and elongated cytoplasmic processes similar to those of normal astrocytes. The level of glial fibrillary acidic protein, an intermediate protein specifically expressed in differentiated astrocytes, was upregulated concomitantly.Conclusions. These findings strongly indicate that exogenous PTEN expression inhibits the proliferation of glioma cells by inducing G1 arrest and elicits astrocytic differentiation in the presence of the ECM. Inactivation of PTEN would play an important role in the enhancement of unregulated growth of undifferentiated glioma cells.

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Genetic alterations in bladder cancer

The Lancet ◽

10.1016/0140-6736(93)91595-d ◽

1993 ◽

Vol 342 (8869) ◽

pp. 469-471 ◽

Cited By ~ 160

Author(s):

G. Dalbagni ◽

J. Presti ◽

W.R. Fair ◽

V. Reuter ◽

C. Cordon-Cardo

Keyword(s):

Bladder Cancer ◽

Genetic Alterations

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The Role of microRNAs in the Regulation of Apoptosis in Lung Cancer and Its Application in Cancer Treatment

BioMed Research International ◽

10.1155/2014/318030 ◽

2014 ◽

Vol 2014 ◽

pp. 1-19 ◽

Cited By ~ 26

Author(s):

Norahayu Othman ◽

Noor Hasima Nagoor

Keyword(s):

Lung Cancer ◽

Cancer Progression ◽

High Frequency ◽

Tumor Suppressor Genes ◽

Molecular Mechanisms ◽

Lung Carcinogenesis ◽

The Past ◽

Late Stage Diagnosis ◽

Anticancer Treatment

Lung cancer remains to be one of the most common and serious types of cancer worldwide. While treatment is available, the survival rate of this cancer is still critically low due to late stage diagnosis and high frequency of drug resistance, thus highlighting the pressing need for a greater understanding of the molecular mechanisms involved in lung carcinogenesis. Studies in the past years have evidenced that microRNAs (miRNAs) are critical players in the regulation of various biological functions, including apoptosis, which is a process frequently evaded in cancer progression. Recently, miRNAs were demonstrated to possess proapoptotic or antiapoptotic abilities through the targeting of oncogenes or tumor suppressor genes. This review examines the involvement of miRNAs in the apoptotic process of lung cancer and will also touch on the promising evidence supporting the role of miRNAs in regulating sensitivity to anticancer treatment.

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The Hippo Pathway: A Master Regulatory Network Important in Cancer

Cells ◽

10.3390/cells10061416 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1416

Author(s):

Qiuping Liu ◽

Xiaomeng Liu ◽

Guanbin Song

Keyword(s):

Metabolic Regulation ◽

Human Cancer ◽

Hippo Pathway ◽

Tumor Development ◽

Biological Significance ◽

Cancer Development ◽

Hippo Signaling ◽

Complex Regulation ◽

And Function ◽

The Hippo Pathway

The Hippo pathway is pervasively activated and has been well recognized to play critical roles in human cancer. The deregulation of Hippo signaling involved in cancer development, progression, and resistance to cancer treatment have been confirmed in several human cancers. Its biological significance and deregulation in cancer have drawn increasing interest in the past few years. A fundamental understanding of the complexity of the Hippo pathway in cancer is crucial for improving future clinical interventions and therapy for cancers. In this review, we try to clarify the complex regulation and function of the Hippo signaling network in cancer development, including its role in signal transduction, metabolic regulation, and tumor development, as well as tumor therapies targeting the Hippo pathway.

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