Rytlewski Jeffrey D, Scalora Nicholas, Garcia Keith, Tanas Munir, Toor Fatima, Miller Benjamin, Allen Bryan, Milhem Mohammed, Monga Varun
Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA.
Department of Pathology, University of Iowa, Iowa City, IA 52242, USA.
Cancers (Basel). 2021 Feb 8;13(4):675. doi: 10.3390/cancers13040675.
Sarcoma is a widely varied and devastating oncological subtype, with overall five-year survival of 65% that drops to 16% with the presence of metastatic disease at diagnosis. Standard of care for localized sarcomas is predicated on local control with wide-local resection and radiation therapy, or, less commonly, chemotherapy, depending on tumor subtype. Verteporfin has the potential to be incorporated into this standard of care due to its unique molecular properties: inhibition of the upregulated Hippo pathway that frequently drives soft tissue sarcoma and photodynamic therapy-mediated necrosis due to oxidative damage. The initial anti-proliferative effect of verteporfin is mediated via binding and dissociation of YAP/TEAD proteins from the nucleus, ultimately leading to decreased cell proliferation as demonstrated in multiple in vitro studies. This effect has the potential to be compounded with use of photodynamic therapy to directly induce cellular necrosis with use of a clinical laser. Photodynamic therapy has been incorporated into multiple malignancies and has the potential to be incorporated into sarcoma treatment.
肉瘤是一种种类繁多且极具破坏性的肿瘤亚型，总体五年生存率为65%，若在诊断时存在转移性疾病，这一比例会降至16%。局部肉瘤的标准治疗方案基于通过广泛局部切除和放射治疗进行局部控制，或者根据肿瘤亚型，较少情况下采用化疗。维替泊芬因其独特的分子特性有潜力被纳入这一标准治疗方案：它能抑制经常驱动软组织肉瘤的上调的Hippo通路，并通过氧化损伤介导光动力疗法诱导的坏死。维替泊芬最初的抗增殖作用是通过YAP/TEAD蛋白从细胞核的结合和解离介导的，最终导致细胞增殖减少，这在多项体外研究中得到了证实。这种效应有可能通过使用临床激光进行光动力疗法直接诱导细胞坏死而得到增强。光动力疗法已被纳入多种恶性肿瘤的治疗，并且有潜力被纳入肉瘤治疗。
