Defining the Triple Negative Breast Cancer Kinome Response to GSK1120212
In this study the investigators want to look at the activity of kinases when a particular
experimental drug called GSK1120212 is administered. GSK1120212 blocks a kinase called MEK.
GSK1120212 is not yet approved by the FDA for use in breast cancer patients. The
investigators want to give subjects GSK1120212 for a short period of time (one week) to see
how MEK and the other kinases function in cancer cells both before and after the study drug
is given. The investigators are giving this drug for research purposes only. The length of
time it is being given is not intended to treat cancer.
Research into treatments for breast cancer relies more and more on an understanding of how
the cells of tumor tissue act when they are exposed to a new or different drug. To find
these new or different drugs to treat cancer, researchers are looking at proteins that help
cancer cells grow, such as a group of proteins called Kinases. This is important because
many of the newest cancer drugs are designed to block kinases causing the cancer cells to
die and the tumors to shrink. However, blocking only one of the kinases at a time is often
less effective than the investigators expected because when you block one kinase another can
take its place. For this reason, the investigators may need to treat breast cancer with
more than one kinase-blocking drug at a time. However, the investigators don't yet know what
the best combination of drugs should be, because it is hard to measure all the possible
kinases. Previous studies have only been able to identify less than 10% of the hundreds of
kinases in cancer cells.
Recently researchers here at UNC have developed a process that can identify may (more than
half) of these kinases. This can tell us which kinases need to be blocked at the same time
to make tumors shrink so that the investigators can design the best combinations of kinase
blocking drugs for triple negative breast cancer. This is especially important for
individuals with triple negative breast cancer (TNBC) because there are fewer drugs
available that can block molecules that affect tumor growth. The investigators believe that
kinase-blocking drugs have the potential to be a more effective treatment for people with
Endpoint Classification: Pharmacodynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science
the number and type of kinases in participant tissue sample prior to administration of drug compared to post-treatment.
use of pan kinase inhibitors immobilized on beads to capture expressed kinases in cells and tumors. The activation state of more than 60% of the expressed kinome, defined by RNA-seq, will be analyzed using mass spectrometry analysis of the captured kinases.
Lisa Carey, MD
UNC Lineberger Comprehensive Cancer Center
United States: Food and Drug Administration
|Lineberger Comprehensive Cancer Center||Chapel Hill, North Carolina 27599-7305|