Researchers have developed a new method: blocking the KRAS cancer-causing gene.

Recently, researchers from the University of North Carolina (UNC) School of Medicine and the University of Texas MD Anderson Cancer Center developed a new way to block the KRAS cancer-causing gene, one of the most common mutant genes in human cancer.
study, led by UNC Associate Professor of Medicine Chad Pecot, offers another way to attack KRAS, a mutation that has proved to be an elusive and frustrating target in drug development.
this new method relies on a specific sequence type of small interference RNA (siRNA).
related findings published in the recent journal MolecularCancer Therapeutics (2014, the latest effect factor 6.107) show that the use of a form of siRNA to block KRAS not only greatly hinders the growth of lung and colon cancer in cultured cells and mice, but also stops cancer metastasis, the leading cause of cancer death. "KRAS has been widely considered a non-drug-based protein, but we found that this is not the case," said Pecot, a
lead author of the paper and a member of the UNC Lineberger Comprehensive Cancer Center.
"KRAS is a signaling molecule --
a protein switch that triggers a series of molecular events that tell cells to grow and survive.
KRAS gene mutation creates a switch that is always "on" and causes cells to divide uncontrollably.
KRAS mutations occur in about 30% of human cancers, especially lung, colon, pancreatic and thyroid cancers. "KraS was one of the first cancer-causing genes to be discovered, and it is a clear target for researchers,"
Pecot said.
people have been trying to attack it for decades, but they are not so lucky.
"suppressing kraS signals has become tricky because it lacks a good "pocket" or "crack" so that small molecules and drugs can be combined.
some researchers have turned to trying to target proteins downstream of the KRAS signal cascade, but these attempts have been limited.
Pecot did not use another traditional method, but decided to use a new genetic tool called RNA interference (RNAi) to destroy the KRAS protein before it was fully formed.
RNAi uses small pieces of engineered RNA, a single-stranded molecule transcribed from DNA, to silence specific genes.
these small pieces of RNA binding to specific genetic information (called mRNAs) into the cells and guiding enzymes to identify this information as enemies.
in this case, these enzymes destroy the genetic information of KRAS mRNA, so KRAS cannot be manufactured.
so cells cannot grow, replicate, or move.
RNAi shows great potential in liver disease, viral infections and cancer treatment.
to see if this method could also defeat kraS cancer genes, Pecot and colleagues first tested different RNA sequences to determine which sequence was most effectively labeled KRAS for destruction.
in a five-segment RNA sequence, the researchers found two candidate sequences that were worth considering for use in cancer models.
when they sent these sequences into tissue culture dating cells, they found that siRNA can destroy more than 90 percent of kraS gene information, significantly weakening the growth of cancer cell strains.
the technology also significantly reduced the number of two signaling molecules (pERK and pMEK) located downstream of KRAS, associated with the proliferation of cancer cells and tumor growth.
next, Pecot and colleagues tested siRNA in mouse models of lung and colon cancer.
they wrapped the sequence in protective lipid nanoparticles and injected siRNA easily into mice.
researchers have found that this treatment can significantly slow the growth of primary tumors.
, for example, tumors from colon cancer models were 69% smaller after treatment with KRAS siRNA than those treated with a controlled RNA sequence.
, the researchers found that silent KRAS can curb the spread of cancer cells to other organs.
in the lung cancer mouse model, siRNA therapy reduced the growth of these secondary malignancies by about 80%, similar to the level in the colon cancer model.
Pecot's findings began with two other studies using siRNA to target KRAS, one from the Frank McCormick Laboratory at the University of California, San Francisco, and the other from the Tyler Jacks Laboratory at the Massachusetts Institute of Technology.
UNC's study is different in that it points out that this approach can be used to control the development of metastatic diseases. "It's encouraging that these three papers appear at about the same time, because it means that if you use unconventional methods, KRAS is medicinal,"
Pecot said.
" Source: Decoding Medicine.