A combination of sorafenib and SC-43 is a synergistic SHP-1 agonist duo to advance hepatocellular carcinoma therapy

Chao, Tzu I.; Tai, Wei-Tien; Hung, Ming-Hui; Tsai, M. H.; Chen, Min Hsuan; Chang, Mao Ju; Shiau, Chung Wai; Chen, Kuen Feng

doi:10.1016/j.canlet.2015.11.039

Cited by 30 publications

(23 citation statements)

References 32 publications

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“…SC-43 is a sorafenib derivative with more anti HCC activity than sorafenib which induces apoptosis in sorafenib-resistant HCC cells. In a recent study conducted by Chao et al [ 33 ], combination of sorfenib with SC-43 to treat HCC patients resulted in decrease p-STAT3 signaling and tumor size and prolonged the survival rate of murine HCC models. Co-administration of TLR3 agonist (lysine-stabilized polyinosinic polycytidylic-acid [poly-ICLC]) with sorafenib could controls HCC progression in vivo and promoted immune activation particularly local NK cells, T cells, macrophages and dendritic cells.…”

Section: Sorafenibmentioning

confidence: 99%

Combinational immune-cell therapy of natural killer cells and sorafenib for advanced hepatocellular carcinoma: a review

Hosseinzadeh¹,

Verdi²,

Ai³

et al. 2018

Cancer Cell Int

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BackgroundHigh prevalence of hepatocellular carcinoma (HCC) and typically poor prognosis of this disease that lead to late stage diagnosis when potentially curative therapies are least effective; therefore, development of an effective and systematic treatment is an urgent requirement.Main bodyIn this review, several current treatments for HCC patients and their advantages or disadvantages were summarized. Moreover, various recent preclinical and clinical studies about the performances of “two efficient agents, sorafenib or natural killer (NK) cells”, against HCC cells were investigated. In addition, the focus this review was on the chemo-immunotherapy approach, correlation between sorafenib and NK cells and their effects on the performance of each other for better suppression of HCC.ConclusionIt was concluded that combinational therapy with sorafenib and NK cells might improve the outcome of applied therapeutic approaches for HCC patients. Finally, it was also concluded that interaction between sorafenib and NK cells is dose and time dependent, therefore, a careful dose and time optimizing is necessary for development of a combinational immune-cell therapy.

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Section: Sorafenibmentioning

confidence: 99%

Combinational immune-cell therapy of natural killer cells and sorafenib for advanced hepatocellular carcinoma: a review

Hosseinzadeh¹,

Verdi²,

Ai³

et al. 2018

Cancer Cell Int

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“…Another novel derivative of Sorafenib, SC-59, when combined with radiotherapy has also shown to be superior to Sorafenib for treating HCC and its actions are mediated through STAT3 inhibition[93]. Last but not least, the synergistic combination of Sorafenib with SC-43, through their SHP-1 agonist effects, has been found efficacious, as it decreased tumor size and improved survival in preclinical models[94]. …”

Section: Sorafenib and Other Chemotherapeutic Drugsmentioning

confidence: 99%

Evolving role of Sorafenib in the management of hepatocellular carcinoma

Ziogas

Tsoulfas

2017

WJCO

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Hepatocellular carcinoma (HCC) is one of the most common malignant diseases worldwide and comes third in cancer-related mortality. Although there is a broad spectrum of treatment options to choose from, only a few patients are eligible candidates to receive a curative therapy according to their stage of disease, and thus palliative treatment is implemented in the majority of the patients suffering from liver cancer. Sorafenib, a multikinase inhibitor, is the only currently approved agent for systemic therapy in patients with advanced stage HCC and early stage liver disease. It has been shown to improve the overall survival, but with various side effects, while its cost is not negligible. Sorafenib has been in the market for a decade and has set the stage for personalized targeted therapy. Its role during this time has ranged from monotherapy to neoadjuvant and adjuvant treatment with surgical resection, liver transplantation and chemoembolization or even in combination with other chemotherapeutic agents. In this review our aim is to highlight in depth the current position of Sorafenib in the armamentarium against HCC and how that has evolved over time in its use either as a single agent or in combination with other therapies.

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“…Sorafenib has been reported to induce cell growth arrest and apoptosis in variety cancers including medulloblastomas [58], pancreatic cancer [59], glioblastoma [60], neuroblastoma [61], acute myeloid leukemia (AML) [62] and hepatocellular carcinoma (HCC) cells [63]. Our group has identified that sorafenib targets STAT3 in a kinase-independent pathway [19] and further generated a series of sorafenib derivatives (SC compounds such as SC-1, SC-40, SC-43, SC-49, SC-60 and SC-78) which lack activities on kinases but effectively induce cell apoptosis in cancers [19,64,65]. Sorafenib is a multiple kinase inhibitor targeting Raf-1 and other tyrosine kinases (e.g., VEGFR2, VEGFR3, Flt-3, PDGFR, and FGFR-1) [66,67].…”

Section: Shp-1/stat3 Pathway Is a Target In The Treatment Of Humanmentioning

confidence: 99%

“…Sorafenib was the first and remains the only approved targeted therapy for advanced HCC in 2016. Comparison with single-agent sorafenib, sorafenib in combination with SC-43 had a synergistic effect on the increment of SHP-1 activity and the decrement of p-STAT3 in HCC cells [64]. In addition, combined sorafenib with SC-43 significantly promoted the apoptotic effect on sorafenib-resistant HCC cells [70].…”

Section: Selective Targeting Shp-1 Is Augmented By Combination Thementioning

confidence: 99%

Alteration of SHP-1/p-STAT3 Signaling: A Potential Target for Anticancer Therapy

Huang

Su²,

Liu

et al. 2017

IJMS

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The Src homology 2 (SH2) domain-containing protein tyrosine phosphatase 1 (SHP-1), a non-receptor protein tyrosine phosphatase, has been reported as a negative regulator of phosphorylated signal transducer and activator of transcription 3 (STAT3) and linked to tumor development. In this present review, we will discuss the importance and function of SHP-1/p-STAT3 signaling in nonmalignant conditions as well as malignancies, its cross-talk with other pathways, the current clinical development and the potential role of inhibitors of this pathway in anticancer therapy and clinical relevance of SHP-1/p-STAT3 in cancers. Lastly, we will summarize and highlight work involving novel drugs/compounds targeting SHP-1/p-STAT3 signaling and combined strategies that were/are discovered in our and our colleagues’ laboratories.

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A combination of sorafenib and SC-43 is a synergistic SHP-1 agonist duo to advance hepatocellular carcinoma therapy

Cited by 30 publications

References 32 publications

Combinational immune-cell therapy of natural killer cells and sorafenib for advanced hepatocellular carcinoma: a review

Combinational immune-cell therapy of natural killer cells and sorafenib for advanced hepatocellular carcinoma: a review

Evolving role of Sorafenib in the management of hepatocellular carcinoma

Alteration of SHP-1/p-STAT3 Signaling: A Potential Target for Anticancer Therapy

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