Department of Immuno-Oncology, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA.
Irell and Manella Graduate School of Biological Sciences, City of Hope, Duarte, CA 91010, USA.
Biomolecules. 2024 Nov 17;14(11):1458. doi: 10.3390/biom14111458.
Desmoplasia is a hallmark feature of pancreatic ductal adenocarcinoma (PDAC) that contributes significantly to treatment resistance. Approaches to enhance drug delivery into fibrotic PDAC tumors continue to be an important unmet need. In this study, we have engineered a tumor-colonizing -based agent that expresses both collagenase and hyaluronidase as a strategy to reduce desmoplasia and enhance the intratumoral perfusion of anticancer agents. Overall, we observed that the tandem expression of both these enzymes by tumor-colonizing resulted in the reduced presence of intratumoral collagen and hyaluronan, which likely contributed to the enhanced chemotherapeutic efficacy observed when used in combination. These results highlight the importance of combination treatments involving the depletion of desmoplastic components in PDAC before or during treatment.
纤维增生是胰腺导管腺癌 (PDAC) 的一个显著特征，它极大地导致了治疗耐药性。增强药物递送至纤维增生性 PDAC 肿瘤中的方法仍然是一个重要的未满足的需求。在这项研究中，我们设计了一种基于肿瘤定植的制剂，该制剂同时表达胶原酶和透明质酸酶，以减少纤维增生并增强抗癌药物在肿瘤内的灌注。总的来说，我们观察到，通过肿瘤定植表达这两种酶，导致肿瘤内胶原和透明质酸的含量减少，这可能有助于联合使用时观察到的化疗效果增强。这些结果强调了在治疗前或治疗期间，通过消耗 PDAC 中的纤维增生成分来进行联合治疗的重要性。
