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Bagaimana sel-sel kanker pankreas menghindari kemoterapi
Salah satu alasan kanker pankreas bisa begitu menantang untuk diobati karena sel-sel tersebut telah menemukan cara untuk menghindari kemoterapi , penelitian menunjukkan ..... Mereka membajak reseptor vitamin D , biasanya terkait dengan kesehatan tulang , dan bertujuan untuk memperbaiki kerusakan yang disebabkan oleh kemoterapi .....read more
How pancreatic
cancer cells sidestep chemotherapy
Date:
January 30, 2015
Source:
Fox Chase Cancer
Center
Summary:
One reason pancreatic
cancer can be so challenging to treat is because its cells have found a way to
sidestep chemotherapy, research shows. They hijack the vitamin D receptor,
normally associated with bone health, and re-purposed it to repair the damage
caused by chemotherapy.
,,,,,,,,,,,,,,,,
pancreatic cancer is one
of the deadliest forms of the disease. The American Cancer Society's most
recent estimates for 2014 show that over 46,000 people will be diagnosed with
pancreatic cancer and more than 39,000 will die from it. Now, research led by
Timothy J. Yen, PhD, Professor at Fox Chase Cancer Center, reveals that one
reason this deadly form of cancer can be so challenging to treat is because its
cells have found a way to sidestep chemotherapy. They hijack the vitamin D
receptor, normally associated with bone health, and re-purposed it to repair
the damage caused by chemotherapy. The findings, which will be published in the
January 3 issue of the journal Cell Cycle, raise
hopes that doctors will one day find a way to turn this process against the
tumor and help chemotherapy do its job.
Most patients diagnosed with pancreatic cancer receive a drug called
gemcitabine, which works by preventing cells from replicating their DNA -- thus
stopping tumor cells from dividing and causing them to die off. Sadly, many patients
die within a few months, often because their cancer finds a way to work around
treatment. But how does that happen? "Maybe there is something we don't
understand about how gemcitabine works," says Dr. Yen. "More likely,
cancer cells have found a way to avoid DNA-damaging drugs."
To determine how pancreatic cancers sidestep chemotherapy and the effects
of gemcitabine, Dr. Yen and his colleagues removed every one of the ~24,000
genes, one by one, in pancreatic cancer cells, exposed the cells to gemcitabine,
and noted which gene "knockout" caused cells to be more sensitive to
the drug.
One of those "knocked-out" genes was particularly important,
namely, the gene for a protein which normally binds to vitamin D. "When we
inactivated this vitamin D receptor in cancer cells and added gemcitabine,
almost all of them died," says Dr. Yen.
That's when the researchers realized they had identified a key mechanism
driving chemotherapeutic effectiveness against pancreatic cancer. "If we
find a drug that inactivates the vitamin D receptor, it may allow gemcitabine
to selectively kill pancreatic cancer cells while leaving healthy cells
unharmed," says Dr. Yen. "Patients would just need to drink lots of
milk or take calcium supplements to make sure their bones stay healthy."
Although the precise role of the vitamin D receptor in pancreatic cancer
remains uncertain, it's clear that pancreatic cancer cells need it, says Dr.
Yen. "Cancer cells are good at finding ways to survive," he explains.
"We suspect that cancer cells hijacked the vitamin D receptor and
reassigned it to perform other cellular functions, such as by repairing DNA
damage caused by gemcitabine so the cancer can continue to divide and
spread."
Although pancreatic cancer cells need the vitamin D receptor to survive,
other normal cells don't, which Yen says is good news for patients because
future cancer treatments can knock out the receptor without causing too much
collateral damage or side effects, as long as patients take calcium supplements
to keep their bones healthy.
"By knocking out the vitamin D receptor, we could inactivate that DNA
repair process that is allowing drug-treated tumor cells to live. As a result,
we could eliminate more cancer cells at the outset," says Dr. Yen.
"The Pancreatic Cancer Action Network has launched an initiative to double
patients' survival by 2020; with this new finding, we believe it's a step in
the right direction."
Story Source:
The above story is based on materials provided by Fox
Chase Cancer Center. Note: Materials may be edited for content and length.
