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Taking down a triple threat with Karmanos and Komen
DETROIT—An infusion of $3.5 million, courtesy of the Susan G. Komen Foundation, will allow researchers at the Barbara Ann Karmanos Cancer Institute to focus on creating better therapies to treat triple-negative breast cancer.
Triple-negative breast cancer, an aggressive form of the disease, is often resistant to standard breast cancer treatments and has a particularly high incidence rate among African Americans and younger women.
Although still in the early stage of research, molecular breast cancer subtypes are used to help researchers plan treatment and develop new therapies. Triple-negative/basal-like cancer is one of four recognized subtypes, and is termed as such because the disease is estrogen receptor-negative, progesterone receptor-negative and HER2/neu-negative.
About 14 to 20 percent of breast cancers are triple-negative or basal-like.
"One of the reasons for the lack of efficacy of current therapies for women with triple-negative breast cancer may be their inability to effectively target the 'cancer stem cell' population," says Dr. Patricia LoRusso, director of the Karmanos Phase I Clinical Trials program and professor of hematology and oncology at Wayne State University School of Medicine. "Recent research has suggested that breast cancers may be driven by a small population of cancer stem cells. These cells, by virtue of their relative resistance to radiation and chemotherapy, may contribute to treatment failure as well as metastasis."
Cancer stem cells are particularly abundant in triple-negative disease; they may also be more frequent in African Americans compared to Caucasian American women. About 26 percent of African American women with breast cancer are triple-negative, compared with 15 percent of Caucasian women. This may account for the aggressive nature of this breast cancer subtype, as well as contribute to racial disparities in outcome. If this is the case, LoRusso explains, then researchers must develop new strategies and novel drugs capable of successfully targeting and destroying the cancer stem cell population.
She adds that the research is a collaborative effort with three institutions. The clinical trials will be led by Karmanos Cancer Institute; the genetic profiling by the Van Andel Research Institute and Translational Genomics Research Institute (TGen); and the cancer stem cell analysis by the University of Michigan Comprehensive Cancer Center.
Dr. Jeffrey Trent, president and research director at Van Andel and TGen, and Dr. Max S. Wicha, distinguished professor of oncology and director of the U-M Comprehensive Cancer Center, will serve along with LoRusso as principal investigators of the grant.
LoRusso has been a Phase I investigator for 21 years with the Barbara Ann Karmanos Cancer Institute and Wayne State University School of Medicine, and possesses extensive experience in primary and secondary evaluation of novel therapeutics. Wicha and Trent are world-renowned in their respective fields of basic/translational science and genomic profiling, respectively.
"We worked hard to form a cross-disciplinary team which includes individuals at multiple institutions who are experts in epidemiologic and health disparities research, laboratory research, clinical research, biostatistics and breast cancer patient advocacy," LoRusso explains.
The grant will fund the testing of three main hypotheses: 1) triple-negative breast cancer is associated with increased levels of cancer stem cells; 2) an increase in the cancer stem cell population in breast cancer of African American as compared to Caucasian American women contributes to the more aggressive biological character, increased incidence of triple-negative breast cancer and poorer outcome; and 3) drugs that inhibit cancer stem cell regulatory pathways will specifically target and reduce cancer stem cell populations in preclinical models, as well as in women with locally advanced and metastatic triple-negative disease.
The hypotheses will be tested in a series of coordinated and integrated laboratory studies and early- phase clinical trials.
LoRusso adds that the Susan G. Komen for the Cure grant process is highly competitive and lengthy. The notice for the Komen Promise award was released in June 2010. The first round of the application, submitted last August, involved scientific peer-review of a short proposal to identify which applicants would be invited to submit full applications.
LoRusso and her collaborators were then invited to submit a full proposal by the beginning of December, which was scientifically peer-reviewed based on Komen's criteria.
Komen supports research that will identify and deliver cures for breast cancer, and has supported every major advance in breast cancer over the past 25 years. Komen is now the largest non-government funder of breast cancer research. The foundation made one grant in 1982, and now funds more than 100 research grants annually. It has invested nearly $450 million in 1,736 research projects, and currently manages a portfolio of 759 active research projects, reflecting a nearly $300 million investment.
Located in mid-town Detroit, the Karmanos Cancer Institute is one of 40 National Cancer Institute-designated comprehensive cancer centers in the United States. It is the only hospital that focuses solely on cancer in the state of Michigan, and treats more than two dozen forms of the disease.