This is really important. Suddenly we have a way to apply known drugs
and methods in a new protocol that at the least partially starves cancer cells
and allows and supports a personalized solution to the cancer crisis. A cure would be nice but this would set the
stage for outright cures using additional protocols when the cancer is slowed
down at least.
The recognition of the importance
of the mitochondria and its outright masking which prevented earlier
recognition surely applies to most other cancers and right away we have a
protocol that at least slows down the progress of the disease even if a cure is
not in the cards.
This may also explain why cancers
in the aged are typically much slower in development.
New “Achilles’ Heel” in Breast Cancer: Tumor Cell Mitochondria
Released: 11/29/2011 4:20 PM EST
Embargo expired: 12/1/2011 9:00 AM EST
Newswise — PHILADELPHIA—Researchers at the Kimmel Cancer Center at
Jefferson (insert www.kimmelcancercenter.org" into "Kimmel Cancer
Center at Jefferson") have identified cancer cell mitochondria as the
unsuspecting powerhouse and “Achilles’ heel” of tumor growth, opening up the
door for new therapeutic targets in breast cancer and other tumor types.
Reporting in the online Dec.1 issue of Cell Cycle, Michael
P. Lisanti, M.D., Ph.D., Professor and Chair of Stem Cell Biology &
Regenerative Medicine at Thomas
Jefferson University, and colleagues provide the first in vivo evidence
that breast cancer cells perform enhanced mitochondrial oxidative
phosphorylation (OXPHOS) to produce high amounts of energy.
“We and others have now shown that cancer is a ‘parasitic disease’
that steals energy from the host—your body,” Dr. Lisanti said, “but this is the
first time we’ve shown in human breast tissue that cancer cell mitochondria are
calling the shots and could ultimately be manipulated in our favor.”
Mitochondria are the energy-producing power-plants in normal cells.
However, cancer cells have amplified this energy-producing mechanism, with at
least five times as much energy-producing capacity, compared with normal cells.
Simply put, mitochondria are the powerhouse of cancer cells and they fuel tumor
growth and metastasis.
The research presented in the study further supports the idea that
blocking this activity with a mitochondrial inhibitor—for instance, an
off-patent generic drug used to treat diabetes known as Metformin—can reverse
tumor growth and chemotherapy resistance. This new concept could radically
change how we treat cancer patients, and stimulate new metabolic strategies for
cancer prevention and therapy.
Investigating the Powerhouse
Whether cancer cells have functional mitochondria has been a hotly debated topic for the past 85 years. It was argued that cancer cells don’t use mitochondria, but instead use glycolysis exclusively; this is known as the Warburg Effect. But researchers at the
To study mitochondria’s role directly, the researchers, including
co-author and collaborator Federica
Sotgia, Assistant Professor in the Department of Cancer Biology, looked at
mitochondrial function using COX activity staining in human breast cancer
samples. Previously, this simple stain was only applied to muscle tissue, a
mitochondrial-rich tissue.
Researchers found that human breast cancer epithelial cells showed
amplified levels of mitochondrial activity. In contrast, adjacent stromal
tissues showed little or no mitochondrial oxidative capacity, consistent with
the new paradigm. These findings were further validated using a computer-based
informatics approach with gene profiles from over 2,000 human breast cancer
samples.
It is now clear that cancer cell mitochondria play a key role in
“parasitic” energy transfer between normal fibroblasts and cancer cells,
fueling tumor growth and metastasis.
“We have presented new evidence that cancer cell mitochondria are at
the heart of tumor cell growth and metastasis,” Dr. Lisanti said. “Metabolically,
the drug Metformin prevents cancer cells from using their mitochondria, induces
glycolysis and lactate production, and shifts cancer cells toward the
conventional ‘Warburg Effect’. This effectively starves the cancer cells to
death”.
Personalized Treatment
Although COX mitochondrial activity staining had never been applied to cancer tissues, it could now be used routinely to distinguish cancer cells from normal cells, and to establish negative margins during cancer surgery. And this is a very cost-effective test, since it has been used routinely for muscle-tissue for over 50 years, but not for cancer diagnosis.
What’s more, it appears that upregulation of mitochondrial activity is
a common feature of human breast cancer cells, and is associated with both
estrogen receptor positive (ER+) and negative (ER-) disease. Outcome analysis
indicated that this mitochondrial gene signature is also associated with an
increased risk of tumor cell metastasis, particularly in ER-negative (ER-)
patients.
“Mitochondria are the ‘Achilles’ heel’ of tumor cells,” Dr. Lisanti
said. “And we believe that targeting mitochondrial metabolism has broad
implications for both cancer diagnostics and therapeutics, and could be
exploited in the pursuit of personalized cancer medicine.”
##
Thomas Jefferson University (TJU), the largest freestanding academic medical center in
References:
Disclosure: Dr. Michael Lisanti serves as on the editorial board of
Cell Cycle. No person at Thomas
Jefferson University
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