Effective management of head and neck cancer (HNC) poses a significant challenge in the field of oncology, due to its intricate pathophysiology and limited treatment options. The most common HNC malignancy is head and neck squamous cell carcinoma (HNSCC). HNSCC treatment includes a combination of surgery, radiation, and chemotherapy. While HNSCC is treatable if diagnosed early, this is often not the case and is considered incurable once in its late stages and metastatic disease has developed. Therapies are also limited once resistant disease has occurred. SP-1-39, a novel colchicine-binding site inhibitor (CBSI), has been recently reported for its potential efficacy in a variety of cancer cell lines including breast, melanoma, pancreatic, and prostate. SP-1-39 also shows abilities to overcome paclitaxel resistance in a paclitaxel-resistant prostate cancer xenograft model. To evaluate the potential of SP-1-39 as a new HNSCC treatment option, herein we systematically performed preclinical studies in HNSCC models using SP-1-39 and demonstrated that, in vitro, SP-1-39 inhibits the proliferation of 2 HNSCC cell lines with low nanomolar IC50 values (1.4 to 2.1 nM), induces HNSCC cell apoptosis in a dose-dependent manner, interferes with migration of HNSCC cells, and leads to HNSCC cell cycle arrest in the G2/M phase. In vivo, SP-1-39 suppresses the primary tumor growth of a Detroit 562 subcutaneous xenograft mouse model in 6- to 8-wk-old, male NSG (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ) mice, with no detectable cytotoxic effects at a low dose of 2.5 mg/kg. This efficacy of SP-1-39 is better when compared with the treatment using a reference chemotherapy drug, paclitaxel at 10 mg/kg. Collectively, these data demonstrate that SP-1-39 is a promising candidate for further development for more efficacious HNSCC treatment.

中文翻译：

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新型抗有丝分裂剂 SP-1-39 抑制头颈部鳞状细胞癌


由于其错综复杂的病理生理学和有限的治疗选择，头颈癌 （HNC） 的有效管理在肿瘤学领域构成了重大挑战。最常见的 HNC 恶性肿瘤是头颈部鳞状细胞癌 （HNSCC）。HNSCC 治疗包括手术、放疗和化疗的组合。虽然 HNSCC 如果及早诊断是可以治疗的，但情况往往并非如此，一旦在晚期和转移性疾病发展，就被认为是无法治愈的。一旦发生耐药性疾病，治疗也会受到限制。SP-1-39 是一种新型秋水仙碱结合位点抑制剂 （CBSI），最近报道了其在多种癌细胞系（包括乳腺癌、黑色素瘤、胰腺癌和前列腺癌）中的潜在疗效。SP-1-39 还显示出在紫杉醇耐药前列腺癌异种移植模型中克服紫杉醇耐药的能力。为了评估 SP-1-39 作为新的 HNSCC 治疗选择的潜力，我们在此使用 SP-1-39 在 HNSCC 模型中系统地进行了临床前研究，并证明，在体外，SP-1-39 抑制 2 种 HNSCC 细胞系的增殖，具有低纳摩尔 IC50 值 （1.4 至 2.1 nM），以剂量依赖性方式诱导 HNSCC 细胞凋亡，干扰 HNSCC 细胞的迁移， 并导致 HNSCC 细胞周期停滞在 G2/M 期。在体内，SP-1-39 抑制 6 至 8 周龄雄性 NSG （NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ） 小鼠，在 2.5 mg/kg 的低剂量下没有可检测的细胞毒作用。与使用 10 mg/kg 的参考化疗药物紫杉醇的治疗相比，SP-1-39 的这种疗效更好。 总的来说，这些数据表明 SP-1-39 是进一步开发更有效的 HNSCC 治疗的有前途的候选者。