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Is Cancer Outwitting ‘Personalized Medicine’?

March 10, 2012

WEDNESDAY, March 7 (HealthDay News) — The genetic makeup of
cancer cells differs significantly from region to region within a single
tumor, according to new research that raises questions about the true
potential of personalized cancer medicine.

With this treatment approach, doctors study a tumor’s genetic makeup to
determine which drugs would work best in a particular patient. But if the
genetic mutations driving the cancer cells vary widely, a single tissue
sample won’t necessarily give the full picture.

This “targeted therapy” involves “sticking a needle into the primary
tumor site and taking a small sliver of a tumor, doing a gene analysis,
and creating a genetic profile of the tumor to predict how the tumor will
behave,” explained Dr. Dan Longo, an oncologist and deputy editor at the
New England Journal of Medicine.

“What this paper tells us is that is an oversimplification of the
complexity of tumors and their heterogeneity,” he said. “If you look at
different sites of the very same tumor and the very same person, one site
might tell you a gene profile associated with a good prognosis and the
other site will tell you a gene profile associated with a bad

Longo wrote an editorial accompanying the new study, published in the
March 8 issue of the New England Journal of Medicine.

In the study, scientists from Cancer Research UK London Research
Institute took 13 biopsies, or tissue samples, from a patient whose kidney
cancer had spread. The biopsies were from eight regions of the kidney
tumor and four tumors in the chest and lungs.

Researchers also took normal tissue, sequenced the patient’s genome and
compared that to what they found in the biopsies.

Genetic analysis turned up 128 mutations in the tumors. But only about
one-third, or about 40 of those mutations, were present in all of the

“The majority of mutations are not shared in every biopsy,” said senior
study author Charles Swanton, a professor of cancer medicine at the
research institute.

Swanton and his colleagues also analyzed tumor tissue samples from
another three patients with kidney cancer. From a total of 30 biopsies
from all four patients, 26 tissue samples had mutations that were highly
heterogenous, or varied, from one another.

Some advances have been made using targeted treatments. Tarceva
(erlotinib) treats non-small-cell lung cancer by inhibiting epidermal
growth factor receptor (EGFR) gene, and Herceptin (trastuzumab) is used to
target breast cancers that are human epidermal growth factor receptor 2

But once cancer has metastasized, it remains notoriously difficult to
treat, Swanton said. “We have not made huge progress in curing advanced
metastatic solid tumors over the last decade, despite the new array of
targeted therapies,” he noted.

The heterogeneity of tumors is likely one reason why, he added.

The targeted drugs that work probably target some ubiquitous, or
common, mutations, such as HER-2 or EGFR. “Different parts of the tumor
can evolve independently,” he said. “What we think is that the drugs that
are working are hitting the mutations that are present at every site of
the disease.”

Moving forward, the key may be figuring out what those common mutations
are and targeting drugs there, he added. But finding those targets will be
challenging, he added. One patient, he said, had three mutations in the
same gene occurring in three regions of the primary tumor. And tumor cells
also develop resistance to medications.

“The level of complexity is sobering in the extreme,” he said.

Dr. Len Lichtenfeld, deputy chief medical officer for the American
Cancer Society, called the research “elegant, important work.”

“Cancer is not just a single mass of tissue that has the same genetic
signature throughout it. There are changes that occur within cancer as it
develops, not only at the primary tumor but elsewhere in the body. This
particular research goes to great lengths to demonstrate how that is in
fact the case,” Lichtenfeld said.

Cancer is incredibly complex, and this study adds another layer to that
complexity, he said. “As we have learned more about cancer cells, we have
learned that as many questions as we answer, as many questions come from
those answers,” he said.

More information

The U.S. National Cancer Institute has more on personalized cancer care.

Article source: http://news.yahoo.com/cancer-outwitting-personalized-medicine-220207304.html


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