Bladder cancer (BC) ranks the fifth among the most prevalent cancers in the United States, with -75,000 new cases diagnosed annually and a 5-year prevalence of over half a million cases. On a per-case basis, BC is the costliest cancer to diagnose and treat. However, in spite of its prevalence, clinical challenges and socioeconomic ramifications, BC is persistently one of the least researched and funded cancers. As a result, the pathogenesis of BC remains poorly understood;few biomarkers exist to reliably predict BC progression;and few novel therapeutics have been developed during the last three decades. Over the last two years, a group of investigators with strong, diverse yet complementary expertise in molecular pathways of BC, chemical carcinogenesis, molecular and cell biology and signal transduction have joined forces to tackle BC using a multidisciplinary approach. Under the leadership of Dr. Xue-Ru Wu, who has been studying bladder biology and cancer for over 24 years, the Team has collaborated closely and synergistically, resulting in the generation of large amounts of preliminary data and testable hypotheses that have laid the foundation for three inter-dependent research projects centering on a common theme - the molecular tumorigenesis for the two major BC pathways: low-grade non-invasive BC versus high-grade invasive BC. This P01 Program is designed to address several critical and pressing problems. What are the combinatorial molecular events that can drive BC formation along the divergent phenotypic pathways and how insights from developing and analyzing genetically engineered mice could benefit BC diagnostics and management (Project 1;P1)? Is acrolein an important carcinogen for tobacco-smoke-caused BC, and are distinct BC pathways underlined by different DNA damage and repair capacities (P2)? And, what are the novel role, upstream regulators, downstream effectors as well as the mechanisms of action of XIAP in BC invasion and progression (P3)? Results from this highly collaborative and synergetic team effort should contribute to the major leap forward in our understanding of the pathogenesis of BC, thus leading to the development of novel biomarkers and therapeutics for this highly prevalent but extremely under-studied disease.
Although bladder cancer (BC) is highly prevalent and very difficult to treat, few concerted efforts exist to study its pathogenesis or discover effective therapies. The interdisciplinary team has built a highly integrated and collaborative program to define the molecular basis of BC formation and progression, which should spawn new, target- and pathway-specific biomarker panels and novel therapeutics.
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|Lee, Hyun-Wook; Park, Sung-Hyun; Weng, Mao-Wen et al. (2018) E-cigarette smoke damages DNA and reduces repair activity in mouse lung, heart, and bladder as well as in human lung and bladder cells. Proc Natl Acad Sci U S A 115:E1560-E1569|
|Wang, Hsiang-Tsui; Lin, Jing-Heng; Yang, Chun-Hsiang et al. (2017) Acrolein induces mtDNA damages, mitochondrial fission and mitophagy in human lung cells. Oncotarget 8:70406-70421|
|Wang, Xing; Zhang, Fenglin; Wu, Xue-Ru (2017) Inhibition of Pyruvate Kinase M2 Markedly Reduces Chemoresistance of Advanced Bladder Cancer to Cisplatin. Sci Rep 7:45983|
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