Bladder cancer, one of the most frequently occurring human cancers, develops via two tracks referred to as papillary and nonpapillary that correspond to clinically different forms of the disease. Most bladder cancers are chemically induced, with tobacco smoking being the leading risk factor. Recent advances in bladder cancer research have enhanced our understanding of the origin of this disease from urothelial progenitor cells via field effects along papillary/luminal and nonpapillary/basal pathways. Evident from the outset of the disease, the diversity of the luminal and basal pathways, together with cell lineage tracing studies, postulates the origin of molecularly distinct subtypes from different uroprogenitor cells. The molecular mechanisms initiating field effects involve a new class of genes referred to as forerunner (FR) genes that generally map around major tumor suppressors such as RB1. These genes are silenced, predominantly by hypermethylation and less frequently by mutations, and drive the expansion of intraurothelial preneoplastic cells. Different FR genes are involved in various molecular subtypes of bladder cancer and they sensitize the uroprogenitor cells to the development of luminal and basal bladder cancers in animal models. In human bladder cancer, luminal and basal forms have dissimilar clinical behavior and response to conventional and targeted chemotherapeutic manipulations. These new research developments hold the promise of expanding our armamentarium of diagnostic and treatment options for patients with bladder cancer and improving our ability to select patients most likely to respond to a specific therapy.

中文翻译：

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膀胱癌的起源。

膀胱癌是最常见的人类癌症之一，它通过两种途径发展，分别称为乳头状癌和非乳头状癌，这与该疾病的临床不同形式相对应。大多数膀胱癌是化学诱导的，吸烟是主要的危险因素。膀胱癌研究的最新进展通过沿乳头/管腔和非乳头/基底途径的场效应，增强了我们对尿路上皮祖细胞起源疾病的认识。从疾病开始就可以明显看出，管腔和基础途径的多样性以及细胞谱系追踪研究推测出了来自不同的尿祖细胞的分子上不同的亚型的起源。启动场效应的分子机制涉及一类称为先行者（FR）基因的新基因，该基因通常在主要的肿瘤抑制因子（如RB1）周围作图。这些基因主要通过高甲基化而沉默，而很少因突变而沉默，并驱动尿路上皮内肿瘤前细胞的扩增。不同的FR基因与膀胱癌的各种分子亚型有关，它们使尿祖细胞对动物模型中的管腔和基底膀胱癌的发展敏感。在人膀胱癌中，管腔和基底形式具有不同的临床行为和对常规和靶向化学治疗操作的反应。