Mekinist (Trametinib) a MEK Kinase inhibitor

[donocco]

We have had discussions on various inhibitors like C-MET (the inhibiting drug is ARK-195) and P13K inhibitors like
BMK-120 which I believe is caled Buparlisib) I found another signal tranduction inhibitor. This inhibits the MEK kinase. There is a pathway where RAS -RAF-MEK-ERK
each abbreviation is a protein kinase, and the one before it stimulates the activity of the one after it. This is downstream signal transduction. After ERK is stimulated the cancer cells are stimulated to proliferate. So the idea of Trametinib is to prevent ERK stimulation by blocking MEK stimulation. In theory this makes sense.

Mekinist (Trametinib) is not experimental but is an FDA approved drug used to treat metastatic melanoma that has a type of BRAF-600K mutation whatever that is. Ill look it up. I studied the drug to see the effect of a MEK inhibitor as Im sure they could eventually find use in breast and other cancers.

The dose of Mekinist is 2mg daily and the patients with metastatic Melanoma who took Mekinist basically lived about four and a half months vs the ones on just IV chemo (either Dacarbazine or Paclitaxel). These patients lived only about 1.5 months.

The list of side effects of Mekinist is long and severe. It can cause severe rashes and if they continue the drug has to be discontinued. It can cause pneumonitis and if the patient develops breathing difficulties the drug has to be discontinued. It can cause retinal detachment, Retinal Vein Occlusion and ultimate blindness. Should visual problems develop the drug has to be discontinued. It can also cause severe heart problems and if the left ventricular ejection fraction is seen to progressively decrease, the drug has to be discontinued.
Other side effects listed for Mekinist are
1. Lymphedema
2. anemia
3 Diarrhea (can be severe and is common)
4. Edema
5 High blood pressure
6. Stomatitis.
7. Bleeding and others.

Ill research some other MEK inhibitors that are in the pipeline and experimental. I certainly hope that this long list of serious side effects is not a general phenomenon with MEK inhibitors. The idea of inhibiting the MEK kinases as a cancer treatment is theoretically sound. Hopefully other MEK inhibitors will be less toxic

Paul