Patel Dutt S, Ahmad Farrukh, Abu Sneineh Majdi, Patel Ravi S, Rohit Reddy Sai, Llukmani Adiona, Hashim Ayat, Gordon Domonick K
Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA.
Emergency Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA.
Cureus. 2021 Feb 18;13(2):e13413. doi: 10.7759/cureus.13413.
Breast cancer management includes a combination of surgery, radiation therapy, and chemotherapy. While this management has proven effective, it is not perfect. To expand the umbrella of management to resistant breast cancer tumors, researchers have explored the idea of sphingosine kinase (SphK) and sphingosine-1-phosphate (S1P) as a potential target for treatment. In this article, we review the mechanism of the sphingosine kinase/sphingosine-1-phosphate (SphK/S1P) axis along with its effect on the tumor microenvironment (TME) and compounds that have been studied inhibiting the SphK/S1P axis. We searched for relevant articles in the last five years in Medline and PubMed Central. Inclusion criteria, exclusion criteria, and quality checklists were applied to identify the most relevant articles. We compiled the information that has been summarized in the respective tables and figures provided in this review. The metabolism of sphingolipids was summarized, followed by the SphK/S1P upregulation in breast cancer cells. The variety of effects by upregulation of SphK led to an increase in inflammation, growth, and metastasis in breast cancer tumors. The increase in S1P also impacted the TME, including the cells and surrounding tissue, allowing the breast tumors to thrive. The final point made was a summary of the compounds and drugs that inhibited the SphK/S1P axis. They have proven their effectiveness and show even greater efficacy in combination with docetaxel and doxorubicin in preclinical studies. In conclusion, what is known about the SphK/S1P axis within breast cancer cells is immense but incomplete as we summarize what is known so far. Having a complete picture will allow a faster transition to application in the clinical field but clinical trials have not commenced as of yet.
乳腺癌的治疗包括手术、放射治疗和化疗的综合应用。虽然这种治疗方法已被证明有效，但并非完美无缺。为了将治疗范围扩大到耐药乳腺癌肿瘤，研究人员探索了将鞘氨醇激酶（SphK）和1-磷酸鞘氨醇（S1P）作为潜在治疗靶点的想法。在本文中，我们综述了鞘氨醇激酶/1-磷酸鞘氨醇（SphK/S1P）轴的作用机制及其对肿瘤微环境（TME）的影响，以及已被研究的抑制SphK/S1P轴的化合物。我们在过去五年的Medline和PubMed Central中搜索了相关文章。应用纳入标准、排除标准和质量检查表来确定最相关的文章。我们整理了本综述中各个表格和图表中总结的信息。总结了鞘脂的代谢，随后是乳腺癌细胞中SphK/S1P的上调。SphK上调产生的多种效应导致乳腺癌肿瘤炎症、生长和转移增加。S1P的增加也影响了TME，包括细胞和周围组织，使乳腺肿瘤得以生长。最后一点是对抑制SphK/S1P轴的化合物和药物的总结。它们已证明了自身的有效性，并且在临床前研究中与多西他赛和阿霉素联合使用时显示出更高的疗效。总之，当我们总结目前已知的情况时，关于乳腺癌细胞内SphK/S1P轴的已知信息很多，但并不完整。全面了解将有助于更快地过渡到临床应用，但截至目前尚未开始临床试验。
