oNs, in order to determine whether the inhibition of mTOR lead or PI3K catalytic and is also in the activation loop by a new, as yet undiscovered regulatory mechanisms. This underlines the need for the design of clinical trials with molecular studies on the correlation with tumor biopsies. As for the new term reps Opportunity profiles of key informants and PI3K RPT evaluates key DNA-PK informants, correlative analyzes are required to identify clinically m Possible and ridiculed Ssliche biomarkers of response and the emergence of resistance. W While PI3K TOR TOR key informants and key informants can m Be more powerful than single agents, their rapalogs gr Te effectiveness lies perhaps in combination with other inhibitors of the pathway.
It is increasingly clear that the antitumor WZ3146 efficacy and duration of response to single-kinase inhibitors are often limited by the parallel signaling pathway activation or bypass the activation of mitogenic signaling pathways comments. Molecular arguments can be k, Check the new digital KIS with MEK or Src inhibitors, farnesyl transferase inhibitors, EGFR or HER2 directed therapies, anti-angiogenic and for ER-positive breast cancer, hormonal agents. As the complexity of t Signaling in cancer is better understood, therapeutic strategies to prevent mTOR with biosynthetic to pivot on the other hand, proliferation and survival of concepts very promising. In this issue of Clinical Cancer Research, Mu oz ? Redondo et al report on the effects of arsenic trioxide on cell lymphocytic leukemia Mie Chronic. Arsenic trioxide has significant antineoplastic properties in vitro and in vivo.
This agent has been widely used in the treatment of acute Promyelozytenleuk Mie used People, but there grew an obstacle to its use in other malignancies h Dermatological diseases and solid tumors, the demand for very high concentrations is toxic, inducing apoptosis in non-APL cells. Mu oz ? Redondo et al show that the ATO induced apoptosis of leukemia is Miezellen inactivation of AKT kinase and blockade of NF-kB and upregulation of PTEN and down-regulation of XIAP. In particular, the ATO treatment of leukemia Found chemistry cells, the activation of JNK, which unerl Ugly excuse for the inactivation of AKT and NFkB and mitochondrial Sch Induce cell death and Leuk’s chemistry. These results extend previous studies that showed an r Crucial and essential for the JNK in the induction of apoptosis in cells ATOdependent APL.
In addition, they put JNK activation from reactive oxygen species in leuk Mix cells, as indicated by experiments in which found a pharmacological inhibitor of JNK or JNK gene silencing to inhibit the formation of ROS was detected miezellen Leuk. Especially the authors of this report show that combinations of two different ATO PI 3-kinase inhibitor, LY294002, and API 2, the result is obtained Hte apoptosis in comparison to treatment with ATO alone. This suggests that combinations of ATO k with PI 3-kinase inhibitors Can a new approach to the leuk Mix sensitize cells