So much cancer research over the years has gone into understanding pathways intrinsic to how tumors grow and spread that much was ignored “about what the immune system is doing or not doing’’ with regard to the cancer, says Lance Miller, PhD, associate professor of cancer biology at Wake Forest School of Medicine.
He and his team use a systems biology approach to understanding how the immune system affects the growth of tumors, and how tumors affect the function of the immune system. In particular, they are studying the gene expression signatures in triple negative breast cancer, a particularly aggressive form of breast cancer.
The results could lead to better treatment options for women with triple negative breast cancer, a type of cancer that is resistant to the most common treatments.
“By examining tumor-immune cell interactions at a systems level, we are gaining new insights into the strengths and weaknesses of both as they battle it out inside cancer patients,’’ Miller says. “The work is already providing clues to what molecules may be key weapons in that battle, and our hope is to attract partners who can help validate these concepts and move them in therapeutic directions.’’
Gene Expression Profiling: A Key to Future Cancer Therapeutics
Miller’s team uses gene expression profiling to better understand how the immune system responds to breast cancer. By studying the expression profiles of 2,000 human breast tumors, Miller and his team identified several immune gene signatures that reflected the abundance and anti-tumor properties of different types of immune cells that fight tumors.
More important, the team learned that in certain aggressive types of breast cancer, such as basal-like or triple negative breast cancer, the immune gene signatures were predictive of cancer recurrence years after initial treatment. Triple negative breast cancer does not express the genes for estrogen receptor, progesterone receptor and Her2/neu; a person with triple negative breast cancer cannot be treated with the most common breast cancer drugs.
Miller and team learned that if the immune gene signatures showed high expression levels, it was a predictor of recurrence-free survival, while low immune gene expression predicted for a high likelihood of recurrence. The results of this research were recently published in the journal Genome Biology. Besides his team at Wake Forest, co-authors include scientists based in Philadelphia, Sweden, Denmark, Belgium and New Zealand.
Potential for Immunotherapeutics
Future directions include:
- Developing a diagnostic test for oncologists to help in devising treatment plans for patients with triple negative breast cancer. Understanding the triple negative breast cancer patient’s immune system, Miller says, can help predict whether chemotherapy would be a useful treatment.
- Working with the Genome Institute of Singapore for the next round of study, the team hopes to attract commercial partners to develop and further test the concepts.
- Patents pending on prognostic gene expression signatures that Miller would like to license and develop with commercial partners.
The ramifications of the next steps are big for triple negative breast cancer alone, much less other possible cancer targets.
There are 235,000 newly diagnosed cases of breast cancer projected in the United States in 2013 by the American Cancer Society. Of those, 15 percent, or about 35,000, will be triple negative. Triple negative breast cancer, which occurs in higher frequency among African-American women, has a higher early mortality rate than other types of breast cancer.
A Future for Immunotherapeutics
Miller says his team’s research “has ramifications that include the discovery of possible immuno-targets in cancer.’’
“We now have a few candidate genes that we believe tumors exploit to escape immune recognition and subsequent elimination. The protein products could become future drug targets.’’
Although his team must confirm its hypotheses, Miller perceives a time in the growing field of immunotherapeutics when patients might receive one of three different types of drugs:
- A drug that enhances the immune cells
- A drug that targets inhibitory immune cells (a kind of rogue immune cell that works against the body’s natural immune defenses)
- A drug that blocks immuno-suppressive signals coming from the tumor
“There’s no question that for cancer therapeutics, I think the rising stars are the immunotherapeutics.’’