• Filter By:
• Specialty
• Source
• Condition
• Cancer
• Infectious Disease
• Drug
• Training
• Management
• Procedure
• Therapy
• Vaccine
• Nutrition
• Country

Co-targeting of ACK1 and KIT triggers additive anti-proliferative and -migration effects in imatinib-resistant gastrointestinal stromal tumors
Biochim Biophys Acta Mol Basis Dis. 2023 Mar 13:166690. doi: 10.1016/j.bbadis.2023.166690. Online ahead of print.ABSTRACTMost gastrointestinal stromal tumors (GIST) harbor mutated receptor tyrosine kinase (RTK) KIT/PDGFRA, which provides an attractive therapeutic target. However, a majority of GISTs ultimately develop resistance to KIT/PDGFRA inhibitor imatinib, multiple therapeutic targets will be identified as a reasonable strategy in imatinib-resistant GISTs. Biological mechanisms of non-RTK activated CDC42 associated kinase 1 (ACK1) are still unclear, which has been found to be activated in GISTs. In the current report...
Source: Biochimica et Biophysica Acta - March 15, 2023 Category: Biochemistry Authors: Wangzhen He Liangliang Xu Jiongyan Ding Li Song Weili Yang Isabella Klooster Daniel F Pilco-Janeta C ésar Serrano Hongming Fang Guojun Jiang Xiaoyan Wang Jiren Yu Wen-Bin Ou Source Type: research

Inhibition of fibroblast growth factor receptor-signaling sensitizes imatinib-resistant gastrointestinal stromal tumors to low doses of topoisomerase II inhibitors
The acquired resistance of gastrointestinal stromal tumors (GISTs) to the targeted-based therapy remains the driving force to identify the novel approaches that are capable of increasing the sensitivity of GISTs to the current therapeutic regimens. Our present data show that BGJ398, a selective fibroblast growth factor receptor (FGFR) inhibitor, sensitizes imatinib (IM)-resistant GIST cells with receptor tyrosine kinase (RTK) switch (loss of c-KIT/gain of pFGFR2a) to the low doses of topoisomerase II inhibitors – doxorubicin (Dox) and etoposide (Eto). Mechanistically, pretreatment of IM-resistant GIST cells with BGJ398 f...
Source: Anti-Cancer Drugs - May 18, 2018 Category: Cancer & Oncology Tags: Preclinical Reports Source Type: research

Opposing roles of KIT and ABL1 in the therapeutic response of gastrointestinal stromal tumor (GIST) cells to imatinib mesylate.
Authors: Rausch JL, Boichuk S, Ali AA, Patil SS, Liu L, Lee DM, Brown MF, Makielski KR, Liu Y, Taguchi T, Kuan SF, Duensing A Abstract Most gastrointestinal stromal tumors (GISTs) are caused by activating mutations of the KIT receptor tyrosine kinase. The small molecule inhibitor imatinib mesylate was initially developed to target the ABL1 kinase, which is constitutively activated through chromosomal translocation in BCR-ABL1-positive chronic myeloid leukemia. Because of cross-reactivity of imatinib against the KIT kinase, the drug is also successfully used for the treatment of GIST. Although inhibition of KIT clea...
Source: Oncotarget - December 16, 2016 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

MTOR inhibition enhances NVP-AUY922-induced autophagy-mediated KIT degradation and cytotoxicity in imatinib-resistant gastrointestinal stromal tumors.
Authors: Hsueh YS, Chang HH, Chiang NJ, Yen CC, Li CF, Chen LT Abstract Our previous study demonstrated NVP-AUY922, a HSP90AA1 inhibitor, could enhance mutant KIT degradation in gastrointestinal stroma tumor (GIST) cells through both proteasome- and autophagy-mediated pathways. Herein, we showed rapamycin, a MTOR inhibitor and autophagy inducer, could reduce total and phospho-KIT expression levels and enhance apoptosis in imatinib-resistant GIST cells. The involvement of autophagy in rapamycin-induced KIT downregulation was further confirmed by co-localization of KIT and autophagosome, and partial recovery of KIT e...
Source: Oncotarget - November 12, 2014 Category: Cancer & Oncology Tags: Oncotarget Source Type: research