UMR 1253, iBrain, Université de Tours, Inserm, Tours, France.
Inserm UMR 1069, Nutrition, Croissance et Cancer (N2C), Université de Tours, Tours, France.
Expert Opin Drug Deliv. 2022 Apr;19(4):421-433. doi: 10.1080/17425247.2022.2061459. Epub 2022 Apr 16.
The combination of microbubbles (MBs) and ultrasound (US) is an emerging method for the noninvasive and targeted enhancement of intratumor chemotherapeutic uptake. This method showed an increased local drug extravasation in tumor tissue while reducing the systemic adverse effects in various tumor models.
We focused on preclinical and clinical studies investigating the therapeutic efficacy and safety of this technology for the treatment of colorectal, pancreatic, and liver cancers. We discussed the limitations of the current investigations and future perspectives.
The therapeutic efficacy and the safety of delivery of standard chemotherapy regimen using MB-assisted US have been mainly demonstrated in subcutaneous models of digestive cancers. Although some clinical trials on pancreatic ductal carcinoma and hepatic metastases from various digestive cancers have shown promising results, successful evaluation of this method in terms of US settings, chemotherapeutic schemes, and MBs-related parameters will need to be addressed in more relevant preclinical models of digestive cancers, in small and large animals before fully and successfully translating this technology for clinic use. Ultimately, a clear evidence of the correlation between the enhanced intratumoral concentrations of therapeutics and the increased therapeutic response of tumors have to be provided in clinical trials.
微泡(MBs)和超声(US)的联合使用是一种新兴的非侵入性和靶向增强肿瘤内化疗药物摄取的方法。该方法在各种肿瘤模型中显示出增加肿瘤组织中局部药物外渗的同时减少了全身不良反应。
我们专注于研究该技术治疗结直肠、胰腺和肝癌的治疗效果和安全性的临床前和临床研究。我们讨论了当前研究的局限性和未来的展望。
使用 MB 辅助 US 递送标准化疗方案的治疗效果和安全性已主要在消化癌的皮下模型中得到证实。尽管一些关于胰腺导管腺癌和来自各种消化系统癌症的肝转移的临床研究显示出了有希望的结果,但在更相关的消化系统癌症的临床前模型中,在小型和大型动物中,需要对这种方法的 US 设置、化疗方案和 MB 相关参数进行成功评估,然后才能将该技术完全成功地转化为临床应用。最终,需要在临床试验中提供治疗药物在肿瘤内浓度增加与肿瘤治疗反应增加之间的相关性的明确证据。