Laboratory of Molecular Cell Biomedicine, Department of Biology, University of the Balearic Islands, 07122 Palma de Mallorca, Spain.
R&D Department, Laminar Pharmaceuticals, C/Isaac Newton, 07121 Palma de Mallorca, Spain.
Int J Mol Sci. 2022 Aug 31;23(17):9902. doi: 10.3390/ijms23179902.
Pancreatic cancer has a high mortality rate due to its aggressive nature and high metastatic rate. When coupled to the difficulties in detecting this type of tumor early and the lack of effective treatments, this cancer is currently one of the most important clinical challenges in the field of oncology. Melitherapy is an innovative therapeutic approach that is based on modifying the composition and structure of cell membranes to treat different diseases, including cancers. In this context, 2-hydroxycervonic acid (HCA) is a melitherapeutic agent developed to combat pancreatic cancer cells, provoking the programmed cell death by apoptosis of these cells by inducing ER stress and triggering the production of ROS species. The efficacy of HCA was demonstrated in vivo, alone and in combination with gemcitabine, using a MIA PaCa-2 cell xenograft model of pancreatic cancer in which no apparent toxicity was evident. HCA is metabolized by α-oxidation to C21:5n-3 (heneicosapentaenoic acid), which in turn also showed anti-proliferative effect in these cells. Given the unmet clinical needs associated with pancreatic cancer, the data presented here suggest that the use of HCA merits further study as a potential therapy for this condition.
由于其侵袭性和高转移性，胰腺癌死亡率很高。当与早期检测这种肿瘤的困难和缺乏有效治疗方法相结合时，这种癌症目前是肿瘤学领域最重要的临床挑战之一。梅尔疗法是一种创新的治疗方法，它基于改变细胞膜的组成和结构来治疗不同的疾病，包括癌症。在这种情况下，2-羟基神经酸（HCA）是一种用于治疗胰腺癌细胞的梅尔治疗剂，通过诱导内质网应激和触发 ROS 物质的产生，诱导这些细胞的程序性细胞死亡（细胞凋亡）。在体内，使用 MIA PaCa-2 胰腺癌细胞异种移植模型，单独使用和与吉西他滨联合使用，证明了 HCA 的疗效，在该模型中没有明显的毒性。HCA 通过α-氧化代谢为 C21:5n-3（二十碳五烯酸），后者也显示出对这些细胞的抗增殖作用。鉴于与胰腺癌相关的未满足的临床需求，这里提出的证据表明，HCA 的使用值得进一步研究，作为这种疾病的一种潜在治疗方法。
