TBBCF Grants $400,000 for Breast Cancer Research

The Terri Brodeur Breast Cancer Foundation has distributed $400,000 to four breast cancer researchers, chosen from 45 grant proposals received for 2016.

Since its inception 10 years ago, the nonprofit has given $3.4 million in 34 grants.

“TBBCF research grants are highly sought as evidenced by the receipt of 45 grant proposals from scientists from all over the United State and Europe,” said John LaMattina, PhD, former President, Pfizer Global Research and Development, who is co-chair of the TBBCF Scientific Advisory Committee (SAC). In 2015, TBBCF received 25 grant proposals. In its 10 years, TBBCF has received 245 proposals in all.

“We received proposals from such distinguished institutions as Dana-Farber Cancer Institute, Memorial Sloan-Kettering Cancer Center, NYU, Yale’s Smilow Cancer Hospital, Mt. Sinai, Cold Spring Harbor Laboratory, Mass General Hospital Cancer Center, Roswell Park, Dartmouth and Yeshiva,” LaMattina said. “This upsurge in proposals is in part due to the successes prior grantees have been having in the war on breast cancer. We had a hard time narrowing down to four winners. If we were able to raise even more grant money, we could have funded five or six as the proposals are that good.”

The vision of the Terri Brodeur Breast Cancer Foundation is to realize effective treatment options to eradicate all types of breast cancer. The Foundation’s core value is that 100 percent of funds raised goes directly to breast cancer research.

The Foundation’s granting process is based on providing support to PhD, MD/PhD and MD physician scientists at early stages of their research careers to enable them to develop independent careers in breast cancer research. The award period is for two years with $50,000 per year.

Annually, these funds are allocated through the efforts of the Foundation’s Scientific Advisory Committee (SAC), which reviews numerous submissions and selects final grant recipients. The Committee members are: Chair, Nicholas Saccomano PhD, Chief Scientific Officer, Array BioPharma, Inc.; Co-chair, John LaMattina, PhD, former President, Pfizer Global Research and Development; and members; Michael Garabedian, PhD, Professor and Course Director, New York University Medical Center; Grants Administrator, Stacey Gualtieri, CPA, President Doherty Beals and Banks; Susan Logan, PhD, Associate Professor, New York University Medical Center; and Mike Morin, PhD, Chief Scientific Officer Onkaido Therapeutic.

We would like to congratulate the four newest research grant recipients:

● Jean Albrengues, PhD, Cold Spring Harbor Laboratory

● Mihriban Karaayvaz, PhD, Mass General Hospital Cancer Center

● Daniel Stover, MD, Dana Farber Cancer Institute

● Eneda Toska, PhD, Memorial Sloan Kettering Cancer Center

Jean Albrengues, PhD, Cold Spring Harbor Laboratory

Dr. Albrengues’ award focuses on the regulation of breast cancer dormancy by the tumor microenvironment. Metastatic breast cancer relapse occurring years after a seemingly successful treatment is preceded by an interlude, termed dormancy, when the cancer remains non-proliferative and undetected at a secondary site. Unfortunately, these dormant tumor cells appear to be refractory to available therapies and the cues mediating their reawakening are largely unknown.

Dr. Albrengues hypothesized that dormant cells are awakened by signals from inflammatory immune cells, which also provide cues for aggressive behavior of cancer cells in the primary tumor.

To test this hypothesis, he will use newly developed in vitro and in vivo models of dormancy and reawakening. To visualize the interactions with the surroundings, the survival, and the proliferation of tumor cells in situ, he will use microscopy in lungs of living mice and determine how these parameters change when the disseminated, dormant tumor cells are induced to reawaken. Using pharmacological and genetic approaches, he will identify and target specific signals between inflammatory and cancer cells during experimental manipulation of dormancy. Together, these approaches will allow him to determine how communications between tumor cells and inflammatory microenvironment contribute to the reawakening and therapy resistance of the dormant cells. This analysis will likely reveal new strategies for treatment of dormant disease.

Dr. Albrengues received his PhD from the University of Nice Sophia-Antipolis in France under the supervision of Dr. Cedric Gaggioli at the Institute for Research on Cancer and Aging, Nice (IRCAN). Using sophisticated three-dimensional assays and in vivo models, he demonstrated, during his doctoral studies, the role of the cytokine LIF and the JAK1/STAT3 signaling pathway during the activation and the epigenetic maintenance of activated pro-invasive fibroblasts. Dr. Albrengues is currently a postdoctoral fellow at Cold Spring Harbor Laboratory in the team of Dr. Mikala Egeblad.

Jean Albrengues, PhD

Mihriban Karaayvaz, PhD, Mass General Hospital Cancer Center

Making a major impact on the incidence and lethality of breast cancer will require a detailed understanding of the early events in breast cancer development, particularly in women who are at the highest risk of developing these cancers such as those who carry mutations in the BRCA1/2 genes. Unfortunately, few breast cancer studies are focused on these early events and on breast cancer prevention. We have established a method to analyze distinct cell populations from healthy mastectomy tissues of BRCA1/2 carriers and from tissues of patients undergoing reduction mammoplasty (non-carrier controls). Through detailed molecular analysis of these tissues, Dr. Karaayvaz will determine the key functional properties of the major breast cell populations in BRCA1/2 carriers compared to controls in order to determine the cause of abnormal function within these cell populations.

Dr. Karaayvaz’ preliminary data have revealed novel mechanisms of luminal progenitor (LP) cell regulation that may suggest a practical way to reverse cancer-associated LP deregulation and thereby decrease breast cancer risk. These studies are likely to have near-term impact, identifying new markers of breast cancer risk and new targets for breast cancer prevention for future clinical trials.

Dr. Karaayvaz obtained her PhD from Stony Brook University, where she studied the role of microRNAs in cancer and discovered a novel microRNA targeting BCL2 and increasing the cytotoxic effect of 5-fluorouracil. Dr. Karaayvaz has a longstanding interest in breast cancer biology and prevention, and is currently a postdoctoral fellow at the Mass General Cancer Center/Harvard Medical School in the laboratory of the Breast Oncology Program Director, Dr. Leif W. Ellisen.

Mihriban Karaayvaz, PhD

Daniel Stover, MD, Dana Farber Cancer Institute

The host immune system is critical in the control and elimination of tumors in many cancer types. In breast cancer, tumor infiltrating immune cells have been associated with both response to chemotherapy and overall outcome for patients. Understanding what immune cell populations infiltrate tumors may help guide which patients are likely to benefit from chemotherapy and provide targets to improve the efficacy of chemo- and other therapies. Within breast cancer, estrogen receptor (ER)-positive breast cancers comprise the majority of all breast cancers but the role of immune cells remains less well-understood relative to other breast cancer subtypes.

We developed evidence that immune cells play a critical role in response to chemotherapy in a subset of patients with ER-positive breast cancers.

As a Terri Brodeur Fellow, Dr. Stover will integrate large, publicly available datasets to investigate immune cell signatures in thousands of breast tumors. In parallel, he will work to understand immune cell subsets in breast cancer biopsies of patients on clinical trials of chemotherapy and immune-directed therapies. Ultimately, his goal is to develop biologically rational, immune-based biomarkers to guide therapy, including chemotherapy and immune-directed therapies.

Dr. Stover is a cum laude graduate of Princeton University and received his MD from Vanderbilt University where he was named to AOA Honor Medical Society. Dr. Stover was a resident in internal medicine at Vanderbilt University Medical Center and was selected to serve as the Hugh J. Morgan Chief Resident in Medicine. He completed his fellowship in medical oncology at the Dana-Farber Cancer Institute/Massachusetts General Hospital/Harvard Cancer Center program. Dr. Daniel Stover is currently an Instructor in Medicine at Dana-Farber Cancer Institute and postdoctoral research fellow in the lab of Joan Brugge, PhD at Harvard Medical School.

Daniel Stover, MD

Eneda Toska, PhD, Memorial Sloan Kettering Cancer Center

Mutations in the PIK3CA gene are the most frequent genomic alterations in estrogen receptor (ER)-positive breast cancers. One treatment strategy is the use of drugs that inhibit the gene’s signaling pathway—however, many patients eventually become resistant to this type of therapy. Further, PI3K signaling pathway inhibition has been shown to increase ER activity, which then increases cells’ dependency on ER and estrogen—fueling growth. However, very little is known about the molecular basis of the crosstalk between the PI3K pathway and ER function.

To better understand this relationship, we have identified genes that both contribute to PI3K inhibition resistance and are necessary for the ER-PI3K crosstalk.

Dr. Toska will explore these newly identified mechanisms of resistance and examine their role on patient biopsies pre-and-on treatment to PI3K inhibitors. With this in mind, she aims to expose new therapeutic targets that could potentially increase treatment success.

Dr. Toska obtained her PhD at University at Buffalo, where she worked under the supervision of Dr. Stefan Roberts. During her doctoral studies, Dr. Toska investigated the mechanisms by which Wilms’ tumor 1 (WT1) regulates transcription and its role in both development and cancer. For her postdoctoral training, she joined Dr. José Baselga’s laboratory, a world leader in breast cancer research, to study the molecular mechanisms that regulate ER function and contribute to resistance to PI3K inhibitors in patients with ER-positive breast cancers.

Eneda Toska, PhD

Please visit www.tbbcf.org for more information about the Foundation, our annual fundraising Walk Across Southeastern CT and for a listing of all TBBCF Fellows and their associated publications “TBBCF Funded Research Grant Publications.”

The Terri Brodeur Breast Cancer Foundation (TBBCF) is a non-profit group committed to fighting breast cancer by directing 100% of gross fundraising dollars directly to breast cancer research. Administrative costs are either sponsor supported or volunteer provided.

The Foundation was established in 2006 by two friends, Norma Logan (1958-2006) and Sandy Maniscalco, who realized the need for a new kind of fundraising organization. It was established to honor Terri Brodeur, who succumbed to the disease in 2005 after a two-year battle with breast cancer. Norma died of breast cancer six months after Terri.

Since 2006, TBBCF has awarded 34 breast cancer researchers $3.4 million in research grants. These awards are intended to support PhD, MD/PhD and MD physician scientists at early stages of their research careers to enable them to develop independent careers in breast cancer research. The Foundation seeks to fund broadly across all relevant disciplines and as such focus areas can include basic, preclinical and clinical research.

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