Heparanase (HPSE)-directed tumor progression plays a crucial role in mediating tumor-host crosstalk and priming the tumor microenvironment, leading to tumor growth, metastasis and chemo-resistance. HPSE-mediated breakdown of structural heparan sulfate (HS) networks in the extracellular matrix (ECM) and basement membranes (BM) directly facilitates tumor growth and metastasis. Lysosome HPSE also induces multi-drug resistance via enhanced autophagy. Therefore, HPSE inhibitors development has become an attractive topic to block tumor growth and metastasis or eliminate drug resistance. In this review, we summarize HPSE inhibitors applied experimentally and clinically according to interaction with the binding sites of HPSE and participation of growth factors. The antitumor activity and structure-activity relationship (SAR) are also emphasized.

乙酰肝素酶（HPSE）指导的肿瘤进展在介导肿瘤宿主串扰和引发肿瘤微环境中起着至关重要的作用，从而导致肿瘤生长，转移和耐药性。HPSE介导的细胞外基质（ECM）和基底膜（BM）中结构硫酸乙酰肝素（HS）网络的分解直接促进了肿瘤的生长和转移。溶酶体HPSE还可通过以下途径诱导多药耐药性自噬增强。因此，HPSE抑制剂的开发已成为阻止肿瘤生长和转移或消除耐药性的诱人话题。在这篇综述中，我们根据与HPSE结合位点的相互作用和生长因子的参与，总结了在实验和临床上应用的HPSE抑制剂。还强调了抗肿瘤活性和结构-活性关系（SAR）。