, ERK1 and ERK2. We Conna T violated Unlike in vivo target ERK1 and ERK2. The development of specific inhibitors of ERK1 and ERK2 is not yet complete and, in the treatment of certain diseases such as Leuk mie, Obtained where Hte ERK activation is associated with a poor prognosis useful. Some tumors are resistant BMS 777607 to inhibitors of MEK because they contain EGFR, KRAS, PI3KCA or PTEN mutations. Some cells with EGFR or KRAS mutation are best Constantly to MEK inhibitors, as well as activate k Can PI3K Akt mTOR pathway Ras. These studies were in vitro demonstrated by using cell lines and in vivo using xenografts also that activation of PI3K and PTEN inactivation not always equivalent in terms of sensitivity to inhibitors. The authors suggest that to be a m Glicher reason k Nnte that PTEN has functions other than the regulation of Akt.
Au Addition these studies showed that the combination of MEK and PI3K pathway inhibitors demonstrated potent approach for certain types of cancer to treat the activation of both pathways had. Only certain types PD-183805 of breast cancers are sensitive to MEK inhibitors. Breast cancer can be classified into three types: luminal breast cancer are usually estrogen receptor-positive and have a relatively good prognosis and the response rate to hormonal therapy for HER2-positive breast cancer who have based poor prognosis if untreated, but are especially sensitive targeting HER2 monoclonal Herceptin body, and basal like breast cancer have a poor prognosis and the lack of expression of HER2, estrogen and progesterone.
Many basal breast cancers express high levels of EGFR to activation of the Ras-Raf MEK ERK cascade. Hoeflich and colleagues found that breast cancer basal cell carcinomas expressed an expression profile as Ras and tested their hypothesis that breast cancer is sensitive to MEK inhibitors, provided that they do not have mutations or PTEN L PI3KCA mixtures. But many luminal and HER2 amplified tumors are best Constantly to MEK inhibitors. They also determined that the loss of PTEN, a negative reaction to Pr Predictor MEK inhibitors. In addition, treatment with MEK inhibitors has often a Erh Increase of activated Akt expression led a justification to consider the effects of adding co PI3K and MEK inhibitors.
The authors also found that the simultaneous administration of MEK and PI3K inhibitors improved to some breast cancer t How it is Sun investigations revealed the Wee et al, and Hoeflich et al that the PI3K Akt mTOR high concept expression confer resistance to MEK inhibitors. These studies continue to illustrate a central concept that we discussed in this review is the r Essential genetics in determining beg Susceptibility to targeted therapy. Other studies have also shown that some tumors with EGFR mutations are resistant to MEK inhibitors. Mutations in the BRAF gene EGFR, KRAS, or chromosome fusion between anaplastic lymphoma kinase tyrosine kinases and ROS are detected in approximately 50 NSCLC. NSCLC cells with BRAF mutations, which are more sensitive to MEK inhibitors. That NSCLC with EGFR mutations, KRAS or ALK chim Re merger between ROS and were This was to determine