ANDI Centre of Excellence for Biomedical and Biomaterials Research (CBBR), University of Mauritius, MSIRI Building, Réduit, Mauritius.
ANDI Centre of Excellence for Biomedical and Biomaterials Research (CBBR), University of Mauritius, MSIRI Building, Réduit, Mauritius.
Cancer Lett. 2015 Dec 28;369(2):266-73. doi: 10.1016/j.canlet.2015.09.007. Epub 2015 Sep 28.
The effectiveness of chemotherapy in PDAC is hampered by the dynamic interaction between stroma and cancer cell. The two opposing schools of thought - non-depletion of the stroma vs its depletion - to better drug efficacy are here discussed. Disrupting stroma-cancer cell interaction to reduce tumor progression and promote apoptosis is identified as the new direction of treatment for PDAC. Clinical data have shown that elimination of fibrosis and blockade of the Hedgehog pathway in stroma effectively promote drug delivery to tumor site and apoptosis. Reduced stiffness of ECM, lower fibrosis, higher permeability and higher blood flow after stroma depletion increase drug delivery. Combination strategies involving selective stroma depletion coupled with chemotherapy is currently proving to be the most efficient at clinical level. Striking the right balance between fibrosis depletion and angiogenesis promotion resulting in enhanced drug delivery and apoptosis is a major challenge. The use of nano drug delivery devices coupled with stroma depletion is emerging as the next phase treatment for PDAC. The breakthrough to combat PDAC will likely be a combination of early diagnosis and the emerging chemotherapy strategies.
化疗在 PDAC 中的疗效受到基质和癌细胞之间动态相互作用的阻碍。这里讨论了两种相反的思想流派——基质非耗竭与耗竭——以提高药物疗效。破坏基质-癌细胞相互作用以减少肿瘤进展和促进细胞凋亡被确定为 PDAC 的新治疗方向。临床数据表明，消除纤维化和阻断基质中的 Hedgehog 通路可有效促进药物递送到肿瘤部位并诱导细胞凋亡。基质耗竭后 ECM 的硬度降低、纤维化减少、通透性和血流增加可提高药物递送效率。目前，联合使用选择性基质耗竭与化疗的策略在临床水平上被证明是最有效的。在纤维化耗竭和血管生成促进之间取得适当平衡，从而增强药物递送和细胞凋亡是一个主要挑战。利用纳米药物递送装置结合基质耗竭正在成为 PDAC 的下一阶段治疗方法。抗击 PDAC 的突破可能是早期诊断和新兴化疗策略的结合。
