Spring Bryan Q, Rizvi Imran, Xu Nan, Hasan Tayyaba
Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Photochem Photobiol Sci. 2015 Aug;14(8):1476-91. doi: 10.1039/c4pp00495g. Epub 2015 Apr 9.
Many modalities of cancer therapy induce mechanisms of treatment resistance and escape pathways during chronic treatments, including photodynamic therapy (PDT). It is conceivable that resistance induced by one treatment might be overcome by another treatment. Emerging evidence suggests that the unique mechanisms of tumor cell and microenvironment damage produced by PDT could be utilized to overcome cancer drug resistance, to mitigate the compensatory induction of survival pathways and even to re-sensitize resistant cells to standard therapies. Approaches that capture the unique features of PDT, therefore, offer promising factors for increasing the efficacy of a broad range of therapeutic modalities. Here, we highlight key preclinical findings utilizing PDT to overcome classical drug resistance or escape pathways and thus enhance the efficacy of many pharmaceuticals, possibly explaining the clinical observations of the PDT response to otherwise treatment-resistant diseases. With the development of nanotechnology, it is possible that light activation may be used not only to damage and sensitize tumors but also to enable controlled drug release to inhibit escape pathways that may lead to resistance or cell proliferation.
在长期治疗过程中,包括光动力疗法(PDT)在内的许多癌症治疗方式都会诱导产生治疗抗性机制和逃逸途径。可以想象,一种治疗诱导的抗性可能会被另一种治疗克服。新出现的证据表明,光动力疗法所产生的肿瘤细胞和微环境损伤的独特机制可用于克服癌症耐药性、减轻生存途径的代偿性诱导,甚至使耐药细胞对标准疗法重新敏感。因此,抓住光动力疗法独特特征的方法为提高多种治疗方式的疗效提供了有前景的因素。在这里,我们重点介绍利用光动力疗法克服经典耐药性或逃逸途径从而提高多种药物疗效的关键临床前研究结果,这可能解释了光动力疗法对其他耐药疾病反应的临床观察结果。随着纳米技术的发展,光激活不仅有可能用于损伤肿瘤并使其敏感化,还能实现可控药物释放,以抑制可能导致耐药性或细胞增殖的逃逸途径。