Browsing by Author "Jamyuang C."

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    Combining the SMAC mimetic LCL161 with Gemcitabine plus Cisplatin therapy inhibits and prevents the emergence of multidrug resistance in cholangiocarcinoma
    (2022-11-30) Prasopporn S.; Suppramote O.; Ponvilawan B.; Jamyuang C.; Chanthercrob J.; Chaiboonchoe A.; More-Krong P.; Kongsri K.; Suntiparpluacha M.; Chanwat R.; Korphaisarn K.; Okada S.; Sampattavanich S.; Jirawatnotai S.; Mahidol University
    Cholangiocarcinoma (CCA) is a highly lethal gastrointestinal malignancy that has one of the worst prognoses among solid tumors. The combination of Gemcitabine + Cisplatin (GEM/CIS) remains the standard first-line treatment for advanced stage CCA. However, this drug combination yields only a modest objective response rate, and in cases that initially respond to this treatment, drug resistance commonly rapidly develops. To improve the efficiency of GEM/CIS therapy for CCA, a thorough understanding of the mechanism of GEM/CIS resistance in CCA is required. To that end – in this study, we developed several acquired GEM/CIS-resistant CCA cell lines and we screened those cell lines for acquired vulnerability. The screening process revealed that subset of CCA with GEM/CIS resistance acquired vulnerability to the small-molecule second mitochondrial-derived activator of caspases (SMAC) mimetics LCL161 and Birinapant. The observed acquired vulnerability was found to be associated with upregulation of an inhibitor of apoptosis protein 2 (cIAP2), a known target of SMAC mimetics. LCL161 or cIAP2-shRNA downregulated cIAP2 and restored the sensitivity to GEM/CIS in GEM/CIS-resistant CCA cell lines and in in vivo GEM/CIS-resistant xenograft models. A strong synergic effect was observed when LCL161 was added to GEM/CIS. Interestingly, this synergism was also observed in drug-naïve CCA cell lines, xenografts, and patient-derived organoids. This triplet therapy also prevented the emergence of multidrug-resistant CCA in in vitro and in vivo models. Our findings suggest that activation of cIAP2 allows CCA to escape GEM/CIS, and that suppression of cIAP2 reestablishes the apoptotic profile of CCA, thus restoring its vulnerability to GEM/CIS. The results of this study indicate that combining the SMAC mimetic LCL161 with GEM/CIS inhibits and prevents the emergence of multidrug resistance in CCA.
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    Corrigendum: Combining the SMAC mimetic LCL161 with Gemcitabine plus Cisplatin therapy inhibits and prevents the emergence of multidrug resistance in cholangiocarcinoma(Front. Oncol., (2022), 12, (1021632), 10.3389/fonc.2022.1021632)
    (2023-01-06) Prasopporn S.; Suppramote O.; Ponvilawan B.; Jamyuang C.; Chanthercrob J.; Chaiboonchoe A.; More-Krong P.; Kongsri K.; Suntiparpluacha M.; Chanwat R.; Korphaisarn K.; Okada S.; Sampattavanich S.; Jirawatnotai S.; Mahidol University
    In the published article, there was an error in the Funding statement. There was one missing funding agency from our manuscript. The correct Funding statement appears below.Funding This study was funded by grants from the National Science and Technology Development Agency (NSTDA) of Thailand, the Japan Science and Technology Agency, and the National Institute of Allergy and Infectious Diseases of the United States as part of the e-ASIA Joint Research Program (e-ASIA JRP); the NSTDA (P-15- 50208), the National Research Council of Thailand (NRCT) R016441034, the Advanced Research in Pharmacology Fund, Siriraj Foundation (D003421), and by Mahidol University (Basic Research Fund, and the grant of fiscal year 2022). The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.