The novel Oxathiazinane derivative GP-2250 (Misetionamide) displays antineoplastic activity in vitro and in vivo, as previously shown in pancreatic cancer cells and in patient-derived mouse xenografts (PDX). Currently, GP 2250 is under phase I clinical trial in pancreatic ductal adenocarcinoma (PDAC). GP-2250 in combination with Gemcitabine displays a high synergistic capacity in various primary and established pancreatic cancer cell lines. Additionally, in the eight PDX models tested, the drug combination was superior in reducing tumor volume with an aggregate tumor regression (ATR) of 74% compared to Gemcitabine alone (ATR: 10%). Similarly, in a PDX maintenance setting following two weeks of treatment with nab-Paclitaxel plus Gemcitabine, the combination of GP-2250 plus Gemcitabine resulted in outstanding tumor control (ATR: 79%) compared to treatment with Gemcitabine alone (ATR: 60%). Furthermore, GP-2250 reduced the ratio of tumor-initiating CD133+markers on the surface of PDAC cells in spheroid cultures, indicating a possible mechanism for the synergistic effect of both substances. Considering the high tolerability of GP 2250, these results may open up a new approach to maintenance therapy with GP-2250/Gemcitabine combination following nab-Paclitaxel plus Gemcitabine as first-line treatment.
新型氧杂噻嗪烷衍生物GP-2250（米塞替酰胺）在体外和体内均显示出抗肿瘤活性，此前已在胰腺癌细胞和患者来源的小鼠异种移植瘤（PDX）模型中得以证实。目前，GP-2250正处于针对胰腺导管腺癌（PDAC）的I期临床试验阶段。在多种原代及已建立的胰腺癌细胞系中，GP-2250与吉西他滨联用显示出高度协同效应。此外，在测试的八种PDX模型中，联合用药方案在缩小肿瘤体积方面表现更优，总体肿瘤消退率（ATR）达74%，而单用吉西他滨仅为10%。同样，在经白蛋白结合型紫杉醇联合吉西他滨治疗两周后的PDX维持治疗中，GP-2250联合吉西他滨方案展现出卓越的肿瘤控制效果（ATR：79%），显著优于单用吉西他滨（ATR：60%）。值得注意的是，GP-2250能降低PDAC细胞球状培养物表面肿瘤起始标志物CD133+的比例，这提示了两种药物协同作用的潜在机制。鉴于GP-2250良好的耐受性，这些研究结果可能为白蛋白结合型紫杉醇联合吉西他滨一线治疗后，采用GP-2250/吉西他滨联合方案进行维持治疗开辟新途径。
肿瘤(癌症)患者之家