The extracellular matrix (ECM) is composed of complex fibrillar proteins, proteoglycans, and macromolecules, generated by stromal, immune, and cancer cells. The components and organisation of the matrix evolves as tumours progress to invasive disease and metastasis. In many solid tumours, dense fibrotic ECM has been hypothesised to impede therapy response by limiting drug and immune cell access. Interventions to target individual components of the ECM, collectively termed the matrisome, have, however, revealed complex tumour-suppressor, tumour-promoter, and immune-modulatory functions, which have complicated clinical translation. The degree to which distinct components of the matrisome can dictate tumour phenotypes and response to therapy is the subject of intense study. A primary aim is to identify therapeutic opportunities within the matrisome, which might support a better response to existing therapies. Many matrix signatures have been developed which can predict prognosis, immune cell content, and immunotherapy responses. In this review, we will examine key components of the matrisome which have been associated with advanced tumours and therapy resistance. We have primarily focussed here on targeting matrisome components, rather than specific cell types, although several examples are described where cells of origin can dramatically affect tumour roles for matrix components. As we unravel the complex biochemical, biophysical, and intracellular transduction mechanisms associated with the ECM, numerous therapeutic opportunities will be identified to modify tumour progression and therapy response.
细胞外基质由复杂的纤维蛋白、蛋白聚糖和大分子组成，这些成分由基质细胞、免疫细胞及癌细胞产生。随着肿瘤进展为侵袭性疾病并发生转移，基质的组成与结构亦随之演变。在许多实体瘤中，致密纤维化的细胞外基质被认为通过限制药物和免疫细胞渗透而阻碍治疗反应。然而，针对细胞外基质各组分（统称为基质组）的干预措施揭示了其复杂的肿瘤抑制、肿瘤促进及免疫调节功能，这些复杂性使临床转化面临挑战。基质组中不同组分能在多大程度上决定肿瘤表型及治疗反应，已成为当前研究的热点。主要研究目标在于识别基质组内的治疗靶点，以期提升现有疗法的应答效果。目前已开发出多种能够预测预后、免疫细胞含量及免疫治疗反应的基质特征谱。本综述将重点探讨与晚期肿瘤及治疗耐药性相关的基质组关键组分。我们主要聚焦于靶向基质组分而非特定细胞类型，但文中也列举了若干案例，说明来源细胞可显著影响基质组分在肿瘤中的作用机制。随着对细胞外基质相关的复杂生化、生物物理及细胞内信号转导机制的深入解析，将发现更多调控肿瘤进展和治疗反应的治疗策略。
Targets in the Tumour Matrisome to Promote Cancer Therapy Response
肿瘤(癌症)患者之家