Huang Lee, Zhai Yougang, Fajardo Cristian D, Lang Deborah
Department of Dermatology, Boston University, Boston, MA 02118, USA.
Cancers (Basel). 2021 Dec 29;14(1):143. doi: 10.3390/cancers14010143.
More options are needed for the effective treatment of melanoma. In a previous study, we discovered the small molecule drug YK-4-279 almost completely inhibited tumor progression in the ;T; transgenic mouse model. YK-4-279 had no effect on tumor initiation but blocked progression of invasive melanoma. Our current study was designed as a treatment model, where YK-4-279 was administered during pigmented lesion formation. The study design included the use of three groups: (1) a control group that received only DMSO without a drug (MOCK), (2) mice following our prior studies with YK-4-279 administered at the time of tumor induction (YK-4-279), and (3) mice treated during tumor initiation (YK-4-279 delay). While the MOCK mice had progression of tumors, both YK-4-279 and YK-4-279 delay groups had a significant block or delay of progression. The majority of mice in the YK-4-279 groups had a block of progression, while the YK-4-279 delay group had either a partial block (60% in male mice or 29% in females) or a delay in disease progression in females (28 days in controls to 50 days in YK-4-279 delay group). Here, we demonstrate that YK-4-279 has a significant impact on blocking or delaying tumor progression in a pre-clinical treatment model of melanoma.
黑色素瘤的有效治疗需要更多选择。在先前的一项研究中,我们发现小分子药物YK-4-279几乎完全抑制了;T;转基因小鼠模型中的肿瘤进展。YK-4-279对肿瘤起始没有影响,但阻断了侵袭性黑色素瘤的进展。我们当前的研究设计为一种治疗模型,在色素沉着病变形成期间给予YK-4-279。研究设计包括使用三组:(1)仅接受不含药物的二甲基亚砜的对照组(模拟组),(2)按照我们先前的研究在肿瘤诱导时给予YK-4-279的小鼠(YK-4-279组),以及(3)在肿瘤起始期间接受治疗的小鼠(YK-4-279延迟组)。虽然模拟组小鼠的肿瘤有进展,但YK-4-279组和YK-4-279延迟组的进展均有显著阻断或延迟。YK-4-279组的大多数小鼠进展被阻断,而YK-4-279延迟组要么有部分阻断(雄性小鼠为60%,雌性小鼠为29%),要么雌性小鼠疾病进展延迟(对照组为28天,YK-4-279延迟组为50天)。在此,我们证明YK-4-279在黑色素瘤的临床前治疗模型中对阻断或延迟肿瘤进展有显著影响。