Abstract:
The tumor stroma, which comprises stromal cells and non-cellular elements, is a critical component of the tumor microenvironment (TME). The dynamic interactions between the tumor cells and the stroma may promote tumor progression and metastasis and dictate resistance to established cancer therapies. Therefore, novel antitumor approaches should combine anticancer and anti-stroma strategies targeting dysregulated tumor extracellular matrix (ECM). ECM remodeling is a hallmark of solid tumors, leading to extensive biochemical and biomechanical changes, affecting cell signaling and tumor tissue three-dimensional architecture. Increased deposition of fibrillar collagen is the most distinctive alteration of the tumor ECM. Consequently, several anticancer therapeutic strategies have been developed to reduce excessive tumor collagen deposition. Herein, we provide an overview of the current advances and challenges of the main approaches aiming at tumor collagen normalization, which include targeted anticancer drug delivery, promotion of degradation, modulation of structure and biosynthesis of collagen, and targeting cancer-associated fibroblasts, which are the major extracellular matrix producers.
摘要:
肿瘤间质,其中包括基质细胞和非细胞元件,是肿瘤微环境(TME)的关键组成部分。肿瘤细胞和基质之间的动态相互作用可以促进肿瘤进展和转移,并指示对已建立的癌症疗法的抗性。因此,新的抗肿瘤方法应结合抗癌和抗基质策略,靶向失调的肿瘤细胞外基质(ECM).ECM重塑是实体瘤的标志,导致广泛的生化和生物力学变化,影响细胞信号传导和肿瘤组织三维结构。纤维状胶原沉积的增加是肿瘤ECM的最独特的改变。因此,已经开发了几种抗癌治疗策略来减少过度的肿瘤胶原沉积。在这里,我们概述了针对肿瘤胶原蛋白正常化的主要方法的当前进展和挑战,其中包括靶向抗癌药物递送,促进退化,胶原蛋白的结构和生物合成的调制,靶向癌症相关的成纤维细胞,是主要的细胞外基质生产者。