A mechanism-based combination therapy reduces local tumor growth and metastasis in an orthotopic model of prostate cancer
A mechanism-based combination therapy reduces local tumor growth and metastasis in an orthotopic model of prostate cancer
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DOI：
10.1158/0008-5472.can-06-1793
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发表时间：
2006-11-15
期刊：
影响因子：
11.2
通讯作者：
Hasan, Tayyaba
中科院分区：
文献类型：
--
作者：
Kosharskyy, Boleslav;Solban, Nicolas;Hasan, Tayyaba
治疗诱导的血管生成分子的刺激可以促进肿瘤血管生成，从而增强肿瘤生长和癌症转移。几种标准和新兴疗法，例如放射疗法和光动力疗法（PDT），可以诱导血管生成分子，从而限制其有效性。 PDT 被批准用于治疗多种癌症；然而，它对血管内皮生长因子（VEGF）的诱导创造了有利于增强肿瘤生长和转移的条件，从而减轻了其细胞毒性和抗血管作用。这是第一份报告表明，前列腺癌原位模型 (LNCaP) 中的亚治愈 PDT 不仅增加了 VEGF 分泌（2.1 倍），而且还增加了淋巴结转移动物的比例。 PDT 随后施用抗血管生成剂 TNP-470，消除了这种增加并减少了局部肿瘤的生长。另一方面，PDT 前施用 TNP-470 在局部肿瘤控制方面效果较差。此外，除PDT+TNP-470组外，所有组中的动物在处死时体重减轻>3g； PDT+TNP-470组动物的体重没有变化。 PDT + TNP-470 组与对照组之间观察到的肿瘤重量和体积显着减少（P < 0.05）表明，以适当的顺序联合使用 PDT 和抗血管生成治疗不仅可以更有效地控制局部肿瘤生长和转移，而且还可以减少与疾病相关的毒性。这种基于分子反应的组合值得进一步研究，因为它们增强了单一疗法并改善了治疗结果。
Therapy-induced stimulation of angiogenic molecules can promote tumor angiogenesis leading to enhanced tumor growth and cancer metastasis. Several standard and emerging therapies, such as radiation and photodynamic therapy (PDT), can induce angiogenic molecules, thus limiting their effectiveness. PDT is approved for the treatment of several cancers; however, its induction of vascular endothelial growth factor (VEGF) creates conditions favorable to enhanced tumor growth and metastasis, therefore mitigating its cytotoxic and antivascular effects. This is the first report showing that subcurative PDT in an orthotopic model of prostate cancer (LNCaP) increases not only VEGF secretion (2.1-fold) but also the fraction of animals with lymph node metastases. PDT followed by administration of an antiangiogenic agent, TNP-470, abolished this increase and reduced local tumor growth. On the other hand, administration of TNP-470 before PDT was less effective at local tumor control. In addition, animals in all groups, except in the PDT + TNP-470 group, had a weight loss of > 3 g at the time of sacrifice; the weight of the animals in the PDT + TNP-470 group did not change. The significant reduction (P < 0.05) in tumor weight and volume observed between the PDT + TNP-470 group and the control group suggests that the combination of PDT and antiangiogenic treatment administered in the appropriate sequence was not only more effective at controlling local tumor growth and metastases but also reduced disease-related toxicities. Such molecular response-based combinations merit further investigations as they enhance both monotherapies and lead to improved treatment outcomes.