Approximately one in 20 people will
develop colorectal cancer in their lifetime, making it the third-most prevalent
form of the disease in the U.S. In Europe, it is the second-most common form of
cancer.
The most widely used first line of
treatment is surgery, but this can result in incomplete removal of the tumor.
Cancer cells can be left behind, potentially leading to recurrence and
increased risk of metastasis. Indeed, while many patients remain cancer-free
for months or even years after surgery, tumors are known to recur in up to 50
percent of cases.
Conventional therapies used to
prevent tumors recurring after surgery do not sufficiently differentiate
between healthy and cancerous cells, leading to serious side effects.
In a paper published today in the
journal Nature Materials, researchers at MIT describe an adhesive patch
that can stick to the tumor site, either before or after surgery, to deliver a
triple-combination of drug, gene, and photo (light-based) therapy.
Releasing this triple combination
therapy locally, at the tumor site, may increase the efficacy of the treatment,
according to Natalie Artzi, a research scientist at MIT's Institute for Medical
Engineering and Science (IMES) and an assistant professor of medicine at
Brigham and Women's Hospital, who led the research.
The general approach to cancer
treatment today is the use of systemic, or whole-body, therapies such as
chemotherapy drugs. But the lack of specificity of anticancer drugs means they
produce undesired side effects when systemically administered.
What's more, only a small portion of
the drug reaches the tumor site itself, meaning the primary tumor is not
treated as effectively as it should be.
Indeed, recent research in mice has
found that only 0.7 percent of nanoparticles administered systemically actually
found their way to the target tumor.
"This means that we are
treating both the source of the cancer—the tumor—and the metastases resulting
from that source, in a suboptimal manner," Artzi says. "That is what
prompted us to think a little bit differently, to look at how we can leverage
advancements in materials science, and in particular nanotechnology, to treat
the primary tumor in a local and sustained manner."
The researchers have developed a
triple-therapy hydrogel patch, which can be used to treat tumors locally. This
is particularly effective as it can treat not only the tumor itself but any
cells left at the site after surgery, preventing the cancer from recurring or
metastasizing in the future.
Firstly, the patch contains gold
nanorods, which heat up when near-infrared radiation is applied to the local
area. This is used to thermally ablate, or destroy, the tumor.
These nanorods are also equipped
with a chemotherapy drug, which is released when they are heated, to target the
tumor and its surrounding cells.
Finally, gold nanospheres that do
not heat up in response to the near-infrared radiation are used to deliver RNA,
or gene therapy to the site, in order to silence an important oncogene in colorectal cancer. Oncogenes are genes that can
cause healthy cells to transform into tumor cells.
The researchers envision that a
clinician could remove the tumor, and then apply the patch to the inner surface
of the colon, to ensure that no cells that are likely to cause cancer
recurrence remain at the site. As the patch degrades, it will gradually release
the various therapies.
The patch can also serve as a
neoadjuvant, a therapy designed to shrink tumors prior to their resection,
Artzi says.
When the researchers tested the
treatment in mice, they found that in 40 percent of cases where the patch was
not applied after tumor removal, the
cancer returned.
But when the patch was applied after
surgery, the treatment resulted in complete remission.
Indeed, even when the tumor was not
removed, the triple-combination therapy alone was enough to destroy it.
Unlike existing colorectal cancer
surgery, this treatment can also be applied in a minimally invasive manner. In
the next phase of their work, the researchers hope to move to experiments in
larger models, in order to use colonoscopy equipment not only for cancer
diagnosis but also to inject the patch to the site of a tumor, when detected.
"This administration modality
would enable, at least in early-stage cancer patients, the avoidance of open
field surgery and colon resection," Artzi says. "Local application of
the triple therapy could thus improve patients' quality of life and therapeutic
outcome."
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