Hope in fight against breast cancer spread to brain

Date: Aug-05-2013A combination of two new therapies already in clinical trials for the treatment of primary malignant brain
tumors may also be effective in the treatment of breast cancer that has spread to the brain, according to US
researchers.

The team, from the University of California Los Angeles (UCLA), demonstrated their new approach, which combines
immunotherapy with gene therapy, in mice. They write about their findings in the August 1st print issue of the journal
Clinical Cancer Research.

Breast cancer is the most common cancer in women. The National Cancer Institute estimates that in the US in 2013
some 235,000 new cases of breast cancer will arise, and the disease will claim some 40,000 lives.

The vast majority of deaths from cancer are because of metastasis, where the cancer spreads from the primary site to
other parts of the body, such as the brain.

Patients with metastatic brain tumors have a very poor prognosis since most current treatments rely on chemotherapy,
and many of the drugs are ineffective because the brain is protected by the blood-brain barrier.

Also, because secondary tumors have a tendency to spring up in several places in the brain, radiation therapy is
also difficult.

Study leader and professor of neurosurgery Carol Kruse told the press their research addresses an "unmet need":

"There is a significant lack of Federally funded research addressing translational studies on brain metastases of
systemic cancers, even though metastatic brain tumors occur ten times more frequently than primary brain tumors in
humans."

For their study the team combined cellular therapy (a type of immunotherapy) and gene therapy.

The cellular therapy uses T cells, known as the foot soldiers of the immune system, that have been primed to kill
breast cancer cells.

The primed T cells are injected into the part of the brain containing the secondary tumor. The researchers observed
how they moved through the brain tissue, recognized and killed the tumor cells.

The gene therapy uses a virus that infects cancer cells and inserts a gene in them. The gene makes the cells
susceptible to a drug called 5-flurocytosine (5-FC) which kills them. The drug is otherwise not toxic to the
patient.

The researchers found each of these therapies reduced metastatic brain tumors in mice, but the tumors shrank even
more when they combined the therapies.

The good news is that the cellular therapy and the gene therapy are already being tested separately in ongoing
clinical trials for primary malignant brain tumors.

The researchers suggest there is a unique opportunity here, to rapidly translate a combination of the two therapies
from the lab to the clinic, for the treatment of breast and other cancers that have spread to the brain.

Earlier this year, researchers revealed how another approach called copper depletion therapy showed surprisingly good
results in preventing the spread of cancer in high-risk triple-negative breast cancer - a form of cancer that is very
difficult to treat.

Written by Catharine Paddock PhD

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