Bond Caroline E, Olson Keaton D, Punar Metehan, Friedman Lillian B, Tang Jian-Hong, Luo Minrui, Bailey Matthew D, Holmgren Robert A, Meade Thomas J
Departments of Chemistry, Molecular Biosciences, Neurobiology, and Radiology, Northwestern University Evanston IL USA
School of Future Technology, University of Chinese Academy of Sciences Beijing 101408 P. R. China.
RSC Adv. 2025 Mar 19;15(11):8572-8579. doi: 10.1039/d5ra00326a. eCollection 2025 Mar 17.
Basal Cell Carcinoma (BCC) is the most frequently diagnosed cancer globally and affects about one in five Americans. Given the frequency of diagnosis, it is surprising that there are very few therapeutic options. Surgical removal is currently the most common treatment option; however, this can lead to noticeable scarring and cosmetic issues. As a result, there is a compelling interest in developing non-invasive therapeutic approaches to this disease. Here, we introduce a new transition metal-DNA derivative called CoGli-GOPEI that inhibits the migration of murine ASZ BCC cells in laboratory experiments. Notably, this complex significantly outperforms two established hedgehog-pathway inhibitors: GANT-61 (an investigational compound) and vismodegib (an FDA-approved drug). These inhibitors target the hedgehog signaling pathway-specifically the Gli family of transcription factors-to slow cancer progression. By effectively reducing cell migration, CoGli-GOPEI offers a less invasive alternative to traditional treatments like surgical resection and chemotherapy. Our results highlight how targeting the Gli transcription factors within the hedgehog pathway can create a novel therapeutic strategy against BCC. The ultimate goal of these new derivates is to reduce the spread of cancer cells while minimizing the downsides of surgery.
基底细胞癌（BCC）是全球诊断出的最常见癌症，约五分之一的美国人受其影响。鉴于其诊断频率之高，令人惊讶的是治疗选择却非常少。手术切除是目前最常见的治疗选择；然而，这可能会导致明显的疤痕和美容问题。因此，开发针对这种疾病的非侵入性治疗方法具有迫切的需求。在此，我们介绍一种名为CoGli-GOPEI的新型过渡金属-DNA衍生物，它在实验室实验中可抑制小鼠ASZ基底细胞癌细胞的迁移。值得注意的是，这种复合物显著优于两种已确立的刺猬信号通路抑制剂：GANT-61（一种研究性化合物）和维莫德吉（一种美国食品药品监督管理局批准的药物）。这些抑制剂靶向刺猬信号通路——特别是转录因子Gli家族——以减缓癌症进展。通过有效减少细胞迁移，CoGli-GOPEI为手术切除和化疗等传统治疗提供了一种侵入性较小的替代方案。我们的结果凸显了靶向刺猬信号通路中的Gli转录因子如何能够创造出一种针对基底细胞癌的新型治疗策略。这些新衍生物的最终目标是减少癌细胞的扩散，同时将手术的负面影响降至最低。
