metronidazole was distributed in pelvic tissues

many of the studies were performed on different established melanoma cell lines which have various additional mutations besides those in BRAF that may or may not be appropriate for real melanomas present in patients. As an example when MEK1 is focused, potent c-Met inhibitor ERK1,2 is inhibited and the negative feed-back loop on MEK is activated and broken MEK accumulates. However, if Raf can also be restricted, it could be possible to totally shut down the pathway. This can be a rationale for treatment with either double Raf/MEK inhibitors or simultaneously with both Raf and MEK individual inhibitors. Moreover targeting equally PI3K and mTOR might be far better than targeting both PI3K or mTOR on their own. This becomes a realistic therapeutic option If it is an individual inhibitor which targets both compounds, such as the new PI3K and mTOR twin inhibitors. Also in some instances it might be required to eliminate the cancer by treatment with a dual PI3K/mTOR inhibitor in addition to with one more PI3K inhibitor which inhibits the PI3K p110 delta isoform as certain dual PI3K/mTOR inhibitors do not efficiently reduce this isoform. Finally, an emerging idea will be the twin targeting of two different signal transduction pathways, Raf/MEK/ERK and PI3K/ PTEN/Akt/mTOR for instance. This has been explored in some clinical trials as well as preclinical models as mentioned in the text. The rationale for the targeting of both pathways might be influenced by the presence of variations in either/or both pathways or in Ras in both pathways can be activated by the particular cancer which. It is not always obvious why a particular mixture of a signal transduction inhibitor and chemotherapeutic drug works in one tumor type but not at all in another tumor type. It has already been experience with the growth of specific chemotherapeutic medications, some work in some cancers however not others. This may derive from a variety of complex connecting activities. Some of these events could include: proportion of cells in different levels of the cell cycle, persistence of CICs, existence of numerous mutated activated oncogene or epigenetic modifications, repressed cyst suppressor genes and a number of other facets. Eventually, supplier AG-1478 chemotherapeutic drug therapy and other styles of therapy may induce certain signaling pathways. The induction of these signalling pathways may counteract some of the consequences of the signal transduction inhibitors. An issue with some of the studies is the fact that most of the immune cells were made after culturing cells in vitro for extended periods of time in the existence of increasing doses of B Raf inhibitors. The clinical relevance of these mechanisms of resistance awaits their identification in samples from melanoma and other cancer patients treated with these inhibitors.