CHAPTER 9 Tumor flare after start of RAF inhibition in KRAS mutated NSCLC
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Ras Effector Mutant Expression Suggest a Negative Regulator Inhibits Lung Tumor Formation
Lung cancer is currently the most deadly malignancy in industrialized countries and accounts for 18% of all cancer-related deaths worldwide. Over 70% of patients with non-small cell lung cancer (NSCLC) are diagnosed at a late stage, with a 5-year survival below 10%. KRAS and the EGFR are frequently mutated in NSCLC and while targeted therapies for patients with EGFR mutations exist, oncogenic K...
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Background PD-1/PD-L1 immune checkpoint pathway mediates tumor evasion from the immune system, and may be associated with poor prognosis in lung cancer. Activating KRAS mutations and LKB1 loss are common mutations in non-small cell lung carcinoma (NSCLC). Patients with mutated KRAS demonstrate less benefit from chemotherapy and resistance to approved targeted therapies. Inactivation of tumor su...
متن کاملMetformin increases antitumor activity of MEK inhibitors through GLI1 downregulation in LKB1 positive human NSCLC cancer cells
PURPOSE Metformin, widely used as antidiabetic drug, showed antitumoral effects expecially in combination with chemotherapy. Our group recently has demonstrated that metformin and gefitinib are synergistic in LKB1-wild-type NSCLC cells. In these models, metformin as single agent induced an activation and phosphorylation of mitogen-activated-protein-kinase (MAPK) through an increased C-RAF/B-RAF...
متن کاملPhase I expansion and pharmacodynamic study of the oral MEK inhibitor RO4987655 (CH4987655) in selected patients with advanced cancer with RAS-RAF mutations.
PURPOSE This phase I expansion study assessed safety, pharmacodynamic effects, and antitumor activity of RO4987655, a pure MEK inhibitor, in selected patients with advanced solid tumor. EXPERIMENTAL DESIGN We undertook a multicenter phase I two-part study (dose escalation and cohort expansion). Here, we present the part 2 expansion that included melanoma, non-small cell lung cancer (NSCLC), a...
متن کاملDifferent metabolic responses to PI3K inhibition in NSCLC cells harboring wild-type and G12C mutant KRAS
KRAS mutations in non-small-cell lung cancer (NSCLC) patients are considered a negative predictive factor and indicate poor response to anticancer treatments. KRAS mutations lead to activation of the PI3K/akt/mTOR pathway, whose inhibition remains a challenging clinical target. Since the PI3K/akt/mTOR pathway and KRAS oncogene mutations all have roles in cancer cell metabolism, we investigated ...
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تاریخ انتشار 2016