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基于生存素的鳞状细胞癌治疗策略。

Survivin-Based Treatment Strategies for Squamous Cell Carcinoma.

机构信息

Department of Clinical Specialistic and Dental Sciences, Marche Polytechnic University, Via Tronto 10, 60126 Ancona, Italy.

Dentistry Clinic, National Institute of Health and Science of Aging, INRCA, 60126 Ancona, Italy.

出版信息

Int J Mol Sci. 2018 Mar 24;19(4):971. doi: 10.3390/ijms19040971.

Abstract

Survivin, an anti-apoptotic molecule abundantly expressed in most human neoplasms, has been reported to contribute to cancer initiation and drug resistance in a wide variety of human tumors. Efficient downregulation of survivin can sensitize tumor cells to various therapeutic interventions, generating considerable efforts in its validation as a new target in cancer therapy. This review thoroughly analyzes up-to-date information on the potential of survivin as a therapeutic target for new anticancer treatments. The literature dealing with the therapeutic targeting of survivin will be reviewed, discussing specifically squamous cell carcinomas (SCCs), and with emphasis on the last clinical trials. This review gives insight into the recent developments undertaken in validating various treatment strategies that target survivin in SCCs and analyze the translational possibility, identifying those strategies that seem to be the closest to being incorporated into clinical practice. The most recent developments, such as dominant-negative survivin mutants, RNA interference, anti-sense oligonucleotides, small-molecule inhibitors, and peptide-based immunotherapy, seem to be helpful for effectively downregulating survivin expression and reducing tumor growth potential, increasing the apoptotic rate, and sensitizing tumor cells to chemo- and radiotherapy. However, selective and efficient targeting of survivin in clinical trials still poses a major challenge.

摘要

Survivin 是一种抗凋亡分子,在大多数人类肿瘤中大量表达,已被报道有助于多种人类肿瘤的癌症起始和耐药性。Survivin 的有效下调可以使肿瘤细胞对各种治疗干预敏感,因此将其作为癌症治疗的新靶点得到了广泛的验证。本综述全面分析了 Survivin 作为新抗癌治疗的治疗靶点的潜力。将对涉及 Survivin 治疗靶向的文献进行综述,特别讨论鳞状细胞癌 (SCC),并重点讨论最近的临床试验。本综述深入了解了在验证针对 SCC 中 Survivin 的各种治疗策略方面所做的最新进展,并分析了转化的可能性,确定了那些似乎最接近纳入临床实践的策略。最近的进展,如显性失活 Survivin 突变体、RNA 干扰、反义寡核苷酸、小分子抑制剂和基于肽的免疫疗法,似乎有助于有效下调 Survivin 表达并降低肿瘤生长潜力,增加细胞凋亡率,并使肿瘤细胞对化疗和放疗敏感。然而,在临床试验中对 Survivin 的选择性和有效靶向仍然是一个重大挑战。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21a4/5979467/f257adeed866/ijms-19-00971-g001.jpg

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