The extracellular matrix (ECM) contributes to tumor progression through changes induced by tumor and stromal cell signals that promote increased ECM density and stiffness. The increase in ECM stiffness is known to promote tumor cell invasion into surrounding tissues and metastasis. In addition, this scar-like ECM creates a protective barrier around the tumor that reduces the effectiveness of innate and synthetic antitumor agents. Herein, clinically approved breast cancer therapies as well as novel experimental approaches that target the ECM are discussed, including in situ hydrogel drug delivery systems, an emerging technology the delivers toxic chemotherapeutics, gene-silencing microRNAs, and tumor suppressing immune cells directly inside the tumor. Intratumor delivery of therapeutic agents has the potential to drastically reduce systemic side effects experienced by the patient and increase the efficacy of these agents. This review also describes the opposing effects of ECM degradation on tumor progression, where some studies report improved drug delivery and delayed cancer progression and others report enhanced metastasis and decreased patient survival. Given the recent increase in ECM-targeting drugs entering preclinical and clinical trials, understanding and addressing the factors that impact the effect of the ECM on tumor progression is imperative for the sake of patient safety and survival outcome.

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原位药物递送至乳腺癌相关的细胞外基质

细胞外基质（ECM）通过由肿瘤和基质细胞信号诱导的变化（促进ECM密度和硬度增加）促进肿瘤进展。已知ECM刚度的增加促进肿瘤细胞侵入周围组织和转移。此外，这种类似疤痕的ECM会在肿瘤周围形成保护性屏障，从而降低先天性和合成性抗肿瘤药的有效性。本文讨论了临床认可的乳腺癌治疗方法以及针对ECM的新型实验方法，包括原位水凝胶药物输送系统是一种新兴技术，可直接在肿瘤内部输送毒性化学疗法，基因沉默的microRNA和抑制肿瘤的免疫细胞。肿瘤内递送治疗剂具有潜在地大大降低患者所经历的全身性副作用并增加这些剂的功效的潜力。这篇综述还描述了ECM降解对肿瘤进展的不利影响，其中一些研究报告了药物输送的改善和癌症进展的延迟，另一些研究报告了转移的增强和患者生存率的降低。鉴于最近进入临床前和临床试验的靶向ECM的药物增多，为了患者安全和生存结果，必须了解和解决影响ECM对肿瘤进展的影响的因素。