is a difficult disease to treat because it's a personal
disease. Each case is unique and based on a combination
of environmental and genetic factors.
what if we had cancer treatments that worked more like a
computer program, which can perform actions based on conditional
statements? Then, a treatment would kill a cell if --and
only if-- the cell had been diagnosed with a mutation. Only
the defective cells would be destroyed, virtually eliminating
unwanted side effects.
a difficult disease to treat because it's a personal disease.
Each case is unique and based on a combination of environmental
and genetic factors. Conventional chemotherapy employs treatment
with one or more drugs, assuming that these medicines are able
to both "diagnose" and "treat" the affected cells. Many of the
side effects experienced by chemotherapy patients are due to the
fact that the drugs they are taking aren't selective enough. For
instance, taking a drug that targets fast-growing tumor cells
frequently results in hair loss, because cells in the hair follicle
are among some of the fastest growing in the body. When it comes
down to it, these drugs get the diagnosis wrong.
But what if
we had cancer treatments that worked more like a computer program,
which can perform actions based on conditional statements? Then,
a treatment would kill a cell if --and only if-- the cell had
been diagnosed with a mutation. Only the defective cells would
be destroyed, virtually eliminating unwanted side effects.
from the National Science Foundation (NSF), researchers at the
California Institute of Technology have created conditional small
RNA molecules to perform this task. Their strategy uses characteristics
that are built into our DNA and RNA to separate the diagnosis
and treatment steps.
are able to detect a mutation within a cancer cell, and then change
conformation to activate a therapeutic response in the cancer
cell, while remaining inactive in cells that lack the cancer mutation,"
claims Niles Pierce, co-author of a recent study which appears
in the September 6 issue of Proceedings of the National Academy
of Sciences (PNAS).
is part of the Molecular Programming Project, funded by NSF's
Directorate for Computer & Information Science & Engineering.
One of the goals of the project is to increase understanding of
how information can be stored and processed by molecules, and
how we might create practical applications that utilize that information.
At the heart
of this approach is ribonucleic acid or RNA, and all of the normal
tasks it performs each and every day to keep our cells alive and
healthy. RNA is the relatively short-lived counterpart of DNA,
the coding system that stores full copies of our entire genome
within almost every cell of our body. If we think of DNA as information
stored on the hard drive of a computer, then RNA is like information
stored on a more volatile kind of memory like RAM -- which is
erased when you switch off your computer.
all kinds of functions in a cell, acting as messengers and switches
to communicate and monitor which genes are expressed in a cell
at any given time. A particular class of RNAs, called small RNAs,
is less than 30 base pairs in length (an average gene is thousands
of base pairs long). These small bits of RNA are involved in many
of the processes that maintain life. The treatment developed by
Pierce and his colleagues relies on two separate small RNAs that
structurally mimic those that occur naturally within our own cells.
Because these molecules resemble small RNAs that are normally
present, the researchers hope there will be few, if any side effects.
diagnosis and treatment, we can create molecules that are both
highly selective and highly effective in killing cancer cells,"
said Pierce. "Conceptually, small conditional RNAs have the potential
to transform cancer treatment because they change what we can
expect from a molecule. Many years of work remain to establish
whether this conceptual promise can be realized in human patients."
it works: Treatment involves two different small RNAS. The first
small RNA will open up if --and only if-- it finds the cancer
mutation. A positive "diagnosis" exposes a signal that was previously
hidden within the small RNA. Once this small RNA is open, a second
small RNA binds to it, setting off a chain reaction in which these
RNA molecules continue to combine to form a longer chain. The
length of the chain is an important part of the "treatment". Longer
chains trick the cell into thinking it has been invaded by a virus,
tripping a self-destruct response.
In the PNAS
study, researchers demonstrated that this approach effectively
eliminates lab-grown human brain, prostate and bone cancer cells
in a mutation-specific manner. Future experiments will determine
whether the treatment is effective on a larger scale.
R. M. Dirks, C. T. Ueda, N. A. Pierce. Selective
cell death mediated by small conditional RNAs.
Proceedings of the National Academy of Sciences, 2010;