UNASSIGNED: @entity320 is known as an exceptionally aggressive and treatment-resistant @entity1 @entity5 . Although a great deal of progress has been made in the past decade, including the development of immunotherapy using immune checkpoint inhibitors and targeted therapy using @entity817 , MEK or KIT inhibitors, treatment for unresectable stage III, stage IV, and recurrent @entity320 is still challenging with limited response rate, severe side effects and poor prognosis, highlighting an urgent need for discovering and designing more effective approaches to conquer @entity320 . @entity320 is not only driven by malignant melanocytes, but also by the altered communication between neoplastic cells and non-malignant cell populations, including fibroblasts, endothelial and inflammatory cells, in the @entity5 stroma. Infiltrated and surrounding fibroblasts, also known as @entity5 -associated fibroblasts (CAFs), exhibit both phenotypical and physiological differences compared to normal dermal fibroblasts. They acquire properties of myofibroblasts, remodel the extracellular matrix (ECM) and architecture of the diseased tissue and secrete chemical factors, which all together promote the transformation process by encouraging @entity5 growth, @entity7499 , @entity32 and @entity3 and contribute to drug resistance. A number of in vitro and in vivo experiments have shown that stromal fibroblasts promote @entity320 cell proliferation and they have been targeted to suppress @entity5 growth effectively. Evidently, a combination therapy co-targeting @entity5 cells and stromal fibroblasts may provide promising strategies to improve therapeutic outcomes and overcome treatment resistance. A significant benefit of targeting CAFs is that the approach aims to create a @entity5 -resistant environment that inhibits growth of @entity320 carrying different genetic mutations. However, the origin of CAFs and precise mechanisms by which CAFs contribute to @entity320 and drug resistance remain poorly understood. In this review, we discuss the origin, activation and heterogeneity of @entity5 microenvironment and examine the contributions of stromal fibroblasts at different stages of @entity320 development. We also highlight the recent progression in dissecting and characterizing how local fibroblasts become reprogrammed and build a dynamic yet optimal microenvironment for @entity5 to develop and @entity3 . In addition, we review key developments in ongoing preclinical studies and clinical applications targeting CAFs and @entity5 -stroma interactions for @entity320 treatment.

Perspective of Targeting Cancer-Associated Fibroblasts in XXXX .

@entity1 :: ('9606', 'Species') :: ['human'] @entity32 :: ('MESH:D007249', 'Disease') :: ['inflammation'] @entity7499 :: ('MESH:D016510', 'Disease') :: ['angiogenesis'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'tumors', 'CAFs in the melanoma tumor', 'cancer'] @entity3 :: ('MESH:D009362', 'Disease') :: ['metastasis', 'metastasize'] @entity817 :: ('673', 'Gene') :: ['BRAF'] @entity320 :: ('MESH:D008545', 'Disease') :: ['melanoma', 'melanoma progression', 'melanomas', 'Melanoma']
@entity320 :: (MESH:D008545,Disease) :: ['Melanoma']
