A new study explores using statins and other medications to treat bladder cancer.
- A new study has identified a protein that helps drive bladder cancer
by triggering the synthesis of cholesterol via mouse and cell models.
- Researchers found that a combination therapy of two drugs disrupts
this pathway, helping to suppress the creation of cancer cells and tumor
growth.
- This combo of medications includes a statin already used for
lowering cholesterol and treating cardiovascular disease in humans.
In 2022, more
than 600,000 people around the world were diagnosed with bladder
cancer, and more than 220,000 people globally died from the disease.
“In 2024, bladder cancer was the fourth most common cancerTrusted
Source diagnosed in men in the U.S., and the eighth most
common cause of death, yet bladder cancer is almost never mentioned as one of
the major cancers, and it is severely understudied,” Tony Hunter,
PhD, American Cancer Society Professor, Renato Dulbecco Chair at the Salk
Institute for Biological Studies in California told Medical News Today.
“While there are new treatments for bladder cancer,
including immune checkpoint therapy, they are not totally effective,
and chemotherapy, radiation, and BCG
(Bacillus Calmette-Guerin) remain the most commonly used treatments,”
Hunter continued. “Clearly, there is an unmet need for new therapeutic
approaches for bladder cancer.”
Hunter is the senior author of a new study recently published
in the journal Cancer Discovery that
has identified a protein they believe helps drive bladder cancer by triggering
the synthesis of cholesterol via both mouse and bladder cancer cell
models.
Researchers also
found that a combination therapy of two drugs — including a statin already
used for lowering cholesterol in humans — disrupts this pathway, suppressing
the creation of cancer cells and tumor growth.
Focusing on the PIN1 protein
For this study, Hunter and his team focused on the
protein PIN1, which has been shown to impact the initiation
and progress of cancer in previous studies.
“PIN1 is an enzyme that is able to alter the local structure
of a protein either increasing or decreasing its activity, but only if a
phosphate has been attached to that protein in a particular place first, which
is then recognized by PIN1,” Hunter explained. “PIN1 is present in all
organisms whose cells have nuclei, from yeast to humans, and its high degree of
conservation during evolution indicates it has an important function.”
PIN1 AND CANCER
“In human cells, PIN1 is known to act
on many target proteins, tweaking their structures once the phosphate signal
has been added by a kinase
enzyme. PIN1 is present at high levels in many cancers, such as breast
cancer, and has been found to activate proteins in multiple intracellular
pathways that drive cancer or inactivate proteins in pathways that normally
block excessive growth.”
— Tony Hunter, PhD
“In bladder cancer, our work shows that PIN1 is important for
bladder cancer cells to proliferate and grow, and to prevent the tumor cells
from committing suicide by a process known as apoptosis,” Hunter added. “PIN1
is also needed for the tumor cells to migrate and invade the surrounding tissue
to form a tumor.”
Combo therapy with statin helps halt bladder cancer tumor growth
Using both animal and bladder cell models, researchers
determined that PIN1 helped direct bladder cancer by triggering the synthesis
of cholesterol.
“The cholesterol we mention is the same chemical as the
cholesterol that we get through our diet, and also the cholesterol that is made
in the liver and enters our circulation,” Hunter said. “Cholesterol is a key
building block of cell membranes and is essential for cell viability. All cells
in the body can make cholesterol for their own use when the local levels of
cholesterol are low, and this is the process that PIN1 is driving in the
bladder cancer cells.”
With a new potential drug target for bladder cancer therapy
identified, the scientists found that a combination of the statin simvastatinTrusted Source and a PIN1 inhibitor called sulfopin helped
stop bladder cancer tumor growth.
STATIN + PIN1
INHIBITOR
“Statins block the synthesis of
cholesterol in (the) liver to lower the level of circulating cholesterol, which
is what is measured when you have a blood draw for a cholesterol test. So
simvastatin is acting in the mouse to block both cholesterol made by the cancer
cells themselves and by the liver, and sulfopin is working in the tumor cells
to decrease synthesis of cholesterol. Together, the combination results in much
lower levels of cholesterol in the bladder cancer tissue, thus reducing tumor
growth.”— Tony Hunter, PhD
Might PIN1-driving cholesterol be a factor in other cancers?
Given that PIN1 levels are high in several other cancers,
Hunter said it is certainly possible that PIN1 may be driving cholesterol
production in other types of cancer.
“Therefore, a PIN1 inhibitor drug given in combination with a
statin to reduce cholesterol production in the tumor cells and decrease
circulating cholesterol produced by the liver might be a viable treatment
option in some other cases,” he continued.
“We plan to follow up on our findings to study the roles of
PIN1 in other cell types in bladder cancer such as fibroblastsTrusted Source, which contribute to the tumor tissue
stromal architecture and to the survival and proliferation of the tumor cells.
We will also survey for other targets for PIN1 that might be important in
bladder cancer cells, including other side-products of the cholesterol
biosynthesis pathway,” Hunter added.
Tip of the iceberg on understanding why cancer grows
MNT had the opportunity to speak
with Jennifer Linehan, MD, a board certified urologist and
associate professor of urology and urologic oncology at Providence Saint John’s
Cancer Institute in Santa Monica, CA, about this study, which she said she
found interesting and hopeful.
“There is so much about why cancer grows, how cancer forms,
that we clearly don’t understand. There [are] definitely actors at play that
are dictating the growth, dictating the invasiveness, that we don’t understand.
And so I think this is just one of (the tips) of the iceberg,” Linehan told MNT.
Linehan said it is important for researchers to continue to
find new ways of treating bladder cancer due to the large surgery required to
treat invasive cancer, and it is one of the more expensive cancers to treat
because it tends to be so recurrent.
THE CHALLENGE OF
TREATING BLADDER CANCER
“Ultimately, especially with invasive
bladder cancer, the treatment is removing the bladder which is an incredibly
big surgery — it is life changing, it is physiologically changing for your
body. If it’s not invasive and it’s recurrent and it keeps coming back, that’s
a lot of toll on the patient themselves, as well as it’s also very costly. The
patient keeps having to come back for checks, keeps having to have different
treatments to keep the cancer at bay.”
— Jennifer Linehan, MD
“Anything that could be curative or stunt (tumor) growth, or
we can manipulate (tumor) growth, is very interesting because a lot of the
treatments that we have now are to kill what you have,” Linehan continued.
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