Taking down a triple threat with Karmanos and Komen

Karmanos Cancer Institute scores $3.5 million Komen Promise grant for breast cancer research

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DETROIT—An infusion of $3.5 million, courtesy of the SusanG. Komen Foundation, will allow researchers at the Barbara Ann Karmanos CancerInstitute to focus on creating better therapies to treat triple-negative breastcancer.
Triple-negative breast cancer, an aggressive form of thedisease, is often resistant to standard breast cancer treatments and has aparticularly high incidence rate among African Americans and younger women.
Although still in the early stage of research, molecularbreast cancer subtypes are used to help researchers plan treatment and developnew therapies. Triple-negative/basal-like cancer is one of four recognizedsubtypes, and is termed as such because the disease is estrogenreceptor-negative, progesterone receptor-negative and HER2/neu-negative.
About 14 to 20 percent of breast cancers are triple-negativeor basal-like.
"One of the reasons for the lack of efficacy of currenttherapies for women with triple-negative breast cancer may be their inabilityto effectively target the 'cancer stem cell' population," says Dr. PatriciaLoRusso, director of the Karmanos Phase I Clinical Trials program and professorof hematology and oncology at Wayne State University School of Medicine."Recent research has suggested that breast cancers may be driven by a smallpopulation of cancer stem cells. These cells, by virtue of their relativeresistance to radiation and chemotherapy, may contribute to treatment failureas well as metastasis."
Cancer stem cells are particularly abundant intriple-negative disease; they may also be more frequent in African Americanscompared to Caucasian American women. About 26 percent of African Americanwomen with breast cancer are triple-negative, compared with 15 percent ofCaucasian women. This may account for the aggressive nature of this breastcancer subtype, as well as contribute to racial disparities in outcome. If thisis the case, LoRusso explains, then researchers must develop new strategies andnovel drugs capable of successfully targeting and destroying the cancer stemcell population. 
She adds that the research is a collaborative effort withthree institutions. The clinical trials will be led by Karmanos CancerInstitute; the genetic profiling by the Van Andel Research Institute andTranslational Genomics Research Institute (TGen); and the cancer stem cell analysisby the University of Michigan Comprehensive Cancer Center.
Dr. Jeffrey Trent, president and research director at VanAndel and TGen, and Dr. Max S. Wicha, distinguished professor of oncology anddirector of the U-M Comprehensive Cancer Center, will serve along with LoRussoas principal investigators of the grant.
LoRusso has been a Phase I investigator for 21 years withthe Barbara Ann Karmanos Cancer Institute and Wayne State University School ofMedicine, and possesses extensive experience in primary and secondaryevaluation of novel therapeutics. Wicha and Trent are world-renowned in theirrespective fields of basic/translational science and genomic profiling,respectively.
"We worked hard to form a cross-disciplinary team whichincludes individuals at multiple institutions who are experts in epidemiologicand 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 cancerstem cells; 2) an increase in the cancer stem cell population in breast cancerof African American as compared to Caucasian American women contributes to themore aggressive biological character, increased incidence of triple-negativebreast cancer and poorer outcome; and 3) drugs that inhibit cancer stem cellregulatory pathways will specifically target and reduce cancer stem cellpopulations in preclinical models, as well as in women with locally advancedand metastatic triple-negative disease.  
The hypotheses will be tested in a series of coordinated andintegrated laboratory studies and early-phase clinical trials.
LoRusso adds that the Susan G. Komen for the Cure grantprocess is highly competitive and lengthy. The notice for the Komen Promiseaward was released in June 2010. The first round of the application, submittedlast August, involved scientific peer-review of a short proposal to identifywhich applicants would be invited to submit full applications. 
LoRusso and her collaborators were theninvited to submit a full proposal by the beginning of December, which wasscientifically peer-reviewed based on Komen's criteria.
Komen supports research that will identify and deliver curesfor breast cancer, and has supported every major advance in breast cancer overthe past 25 years. Komen is now the largest non-government funder of breastcancer research. The foundation made one grant in 1982, and now funds more than100 research grants annually. It has invested nearly $450 million in 1,736research projects, and currently manages a portfolio of 759 active researchprojects, reflecting a nearly $300 million investment.
Located in mid-town Detroit, the Karmanos Cancer Instituteis one of 40 National Cancer Institute-designated comprehensive cancer centersin the United States. It is the only hospital that focuses solely on cancer inthe state of Michigan, and treats more than two dozen forms of the disease. 

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