Figure 14.

Targeting stiffness in primary and metastatic tumour niches. (A) Lysyl oxidase (LOX) inhibitor therapy prevents tumour metastasis by destructing the premetastatic niche, thereby inhibiting cancer cells from colonization. (B) Antiangiogenic therapy for the treatment of metastatic cancer by drugs that target the renin-angiotensin system (RAS), and inactivating metastasis-associated fibroblasts (MAFs), which stimulate angiogenesis in the metastatic niche. (C) Tissue-softening techniques combined with CTL-targeting immunotherapies, such as immune checkpoint inhibitors and chimeric antigen receptor-T (CAR-T) cells, the infiltration of cytotoxic T lymphocytes (CTLs) increases. (D) Recruitment of CTLs into tumour lesions is accompanied by the degradation of tumour ECM by the fusion protein (TNF-CSG), which binds to laminin-nidogen complexes in tumour ECM. (E) Heparanase, an enzyme that breaks down the ECM, is expressed by CAR-T cells, which increases their capacity to penetrate the ECM [156]. Reproduced with permissions from Jeongeun Hyun et al., Trends in Molecular Medicine, Elsevier, 2022.