Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P42345 (mTOR)
 26,049 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

PURPOSE : Treatment effects of advanced gastric cancer (AGC) are unsatisfactory, and novel therapeutic approaches are much needed. The epidermal growth factor receptor (EGFR) monoclonal antibody cetuximab inhibits the growth of several human cancer cells but has been tested rarely for the treatment of GC. The synergy between cetuximab and irinotecan has been reported in colorectal cancer, but the mechanisms are still not fully clarified. Consequently, we hypothesized cetuximab/irinotecan combination should enhance the antitumor activity of irinotecan in GC cells. METHODS : The in vitro antiproliferative, pro-apoptotic, cell cycle arrest effects and induction of senescence were examined in SGC-7901 and MKN-45 GC cell lines. The effects of cetuximab or irinotecan as single agents or the combination on the expression of p53, p16, and EGFR signaling pathways were also studied. RESULTS : The study revealed that cetuximab alone did not show any antiproliferative, pro-apoptotic, cell cycle arrest or cellular senescence effect on GC cells but when combined with irinotecan synergistically inhibits GC cell proliferation and induces apoptosis and G2/M phase arrest. Irinotecan increases phosphorylation of EGFR, MAPK, and AKT and decreases the expression of P27(Kip1), which could be all abrogated by its combination with cetuximab. The combination could also inhibit the expression of Cyclin D1 and phosphorylated mTOR while had no impact on p53, p16, PTEN, and HIF-1alpha. CONCLUSIONS : Cetuximab enhances the activities of irinotecan on GC cells via the downregulation of the EGFR pathway upregulated by irinotecan. Combination therapy with cetuximab and irinotecan, a novel therapeutic approach, warrants further study in GC.
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PMID:Cetuximab enhances the activities of irinotecan on gastric cancer cell lines through downregulating the EGFR pathway upregulated by irinotecan. 2128 18

Hepatoblastoma is the most common primary malignant neoplasm of the liver in children. Improvements in chemotherapy and surgical techniques have increased survival rates for those with localized disease. The prognosis for patients with progressive or relapsed disease continues to be dismal. Complete resection by surgery or liver transplantation is necessary for cure. Few conventional chemotherapy agents have demonstrated activity in progressive or relapsed hepatoblastoma. Irinotecan has shown activity in relapsed and progressive hepatoblastoma. The efficacy of high-dose chemotherapy in this setting is unknown. Newer targeted agents that 'selectively' interfere with pathway targets involved in tumor growth and progression such as insulin-like growth factor, phosphatidylinositol 3-kinase (PI3K), Akt, and mammalian target of rapamycin (mTOR) are currently under development. Because of the rarity of hepatoblastoma, only a small minority of these agents will ever be evaluated in children with this disorder. Gene-directed therapy and immunotherapy have shown promising results in the preclinical setting, and should be investigated as future treatment options for advanced hepatoblastoma.
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PMID:Current and future management strategies for relapsed or progressive hepatoblastoma. 2270 40