SPK1/S1P axis confers gastrointestinal stromal tumors (GISTs) resistance of imatinib

Chen, Yan; Zhang, Rui; Mi, Dandan; Wang, Qiuju; Huang, Tingwenli; Dong, Xinwei; Zhang, Hongwei; Xiao, Hongtao; Shi, Sanjun

doi:10.1007/s10120-022-01332-7

Cited by 2 publications

(1 citation statement)

References 67 publications

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“…S1P is distributed in plasma, blood cells, as well as various cancer tissues [ 16 ]. The production of S1P is confined to two isoforms of kinase enzymes including SphK1 and SphK2 [ 17 , 18 ]. Previous reports addressed elevated levels of sphingosine kinases in various cancer origins such as gastric, breast, pancreatic, and, lung carcinomas [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

The emerging roles of sphingosine 1-phosphate and SphK1 in cancer resistance: a promising therapeutic target

Alkafaas,

Elsalahaty,

Ismail

et al. 2024

Cancer Cell Int

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Cancer chemoresistance is a problematic dilemma that significantly restrains numerous cancer management protocols. It can promote cancer recurrence, spreading of cancer, and finally, mortality. Accordingly, enhancing the responsiveness of cancer cells towards chemotherapies could be a vital approach to overcoming cancer chemoresistance. Tumour cells express a high level of sphingosine kinase-1 (SphK1), which acts as a protooncogenic factor and is responsible for the synthesis of sphingosine-1 phosphate (S1P). S1P is released through a Human ATP-binding cassette (ABC) transporter to interact with other phosphosphingolipids components in the interstitial fluid in the tumor microenvironment (TME), provoking communication, progression, invasion, and tumor metastasis. Also, S1P is associated with several impacts, including anti-apoptotic behavior, metastasis, mesenchymal transition (EMT), angiogenesis, and chemotherapy resistance. Recent reports addressed high levels of S1P in several carcinomas, including ovarian, prostate, colorectal, breast, and HCC. Therefore, targeting the S1P/SphK signaling pathway is an emerging therapeutic approach to efficiently attenuate chemoresistance. In this review, we comprehensively discussed S1P functions, metabolism, transport, and signaling. Also, through a bioinformatic framework, we pointed out the alterations of SphK1 gene expression within different cancers with their impact on patient survival, and we demonstrated the protein–protein network of SphK1, elaborating its sparse roles. Furthermore, we made emphasis on different machineries of cancer resistance and the tight link with S1P. We evaluated all publicly available SphK1 inhibitors and their inhibition activity using molecular docking and how SphK1 inhibitors reduce the production of S1P and might reduce chemoresistance, an approach that might be vital in the course of cancer treatment and prognosis. Graphical Abstract

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Section: Introductionmentioning

confidence: 99%

The emerging roles of sphingosine 1-phosphate and SphK1 in cancer resistance: a promising therapeutic target

Alkafaas,

Elsalahaty,

Ismail

et al. 2024

Cancer Cell Int

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Therapeutic advances of targeting receptor tyrosine kinases in cancer

Tomuleasa,

Tigu,

Munteanu

et al. 2024

Sig Transduct Target Ther

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Receptor tyrosine kinases (RTKs), a category of transmembrane receptors, have gained significant clinical attention in oncology due to their central role in cancer pathogenesis. Genetic alterations, including mutations, amplifications, and overexpression of certain RTKs, are critical in creating environments conducive to tumor development. Following their discovery, extensive research has revealed how RTK dysregulation contributes to oncogenesis, with many cancer subtypes showing dependency on aberrant RTK signaling for their proliferation, survival and progression. These findings paved the way for targeted therapies that aim to inhibit crucial biological pathways in cancer. As a result, RTKs have emerged as primary targets in anticancer therapeutic development. Over the past two decades, this has led to the synthesis and clinical validation of numerous small molecule tyrosine kinase inhibitors (TKIs), now effectively utilized in treating various cancer types. In this manuscript we aim to provide a comprehensive understanding of the RTKs in the context of cancer. We explored the various alterations and overexpression of specific receptors across different malignancies, with special attention dedicated to the examination of current RTK inhibitors, highlighting their role as potential targeted therapies. By integrating the latest research findings and clinical evidence, we seek to elucidate the pivotal role of RTKs in cancer biology and the therapeutic efficacy of RTK inhibition with promising treatment outcomes.

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SPK1/S1P axis confers gastrointestinal stromal tumors (GISTs) resistance of imatinib

Cited by 2 publications

References 67 publications

The emerging roles of sphingosine 1-phosphate and SphK1 in cancer resistance: a promising therapeutic target

The emerging roles of sphingosine 1-phosphate and SphK1 in cancer resistance: a promising therapeutic target

Therapeutic advances of targeting receptor tyrosine kinases in cancer

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