Crosstalk between bladder cancer and the tumor microenvironment: Molecular mechanisms and targeted therapy

<p>Bladder cancer (BCa) is the most common and lethal urological malignancy. Lymphatic metastasis is the main type of metastasis and a poor prognostic factor for bladder cancer patients. Although several treatments are approved for BCa patients, some patients are still resistant to current therapy. The tumor microenvironment (TME), which consists of diverse cellular components, is a crucial mediator of cancer progression and treatment resistance. However, the literature on the interactions between BCa and the TME lacks coherence and systematic analysis, while the impact of intratumoral heterogeneity (ITH) on the tumorigenesis and progression of BCa has not been fully summarized. Iterative insights into factors intrinsic to and extrinsic to BCa cells that regulate metastasis and treatment response are critically needed. Here, we provide an overview of the current knowledge of the multilevel crosstalk between BCa and the TME, including protein-coding genes and epigenetic factors in BCa cells, tumor-associated macrophages (TAMs), cancer-associated fibroblasts (CAFs), tumor-associated neutrophils (TANs), endothelial cells (ECs), lymphatic endothelial cells (LECs) and other cells that play crucial roles in tumorigenesis, progression, and the development of drug resistance. We also summarize the most advanced therapeutic approaches targeting the TME in BCa and discuss some of the challenges and future perspectives associated with TME therapies.</p>