Breast Cancer

Current Projects
Jennifer L. Caswell-Jin, MD

The development of HER2-targeted therapies over the past two decades has had tremendous positive impact on the lives of HER2-positive breast cancer patients. However, tumor resistance to these therapies remains a significant challenge: a sizable portion of patients with early-stage HER2-positive breast cancer develop recurrence, and the vast majority of patients with metastatic HER2-positive breast cancer eventually progress through treatment. Jennifer proposes to construct a model of HER2-positive breast cancer evolution that will reveal how the cancer changes over time when treated with HER2-targeted therapy. She will examine each tumor at multiple time points in the course of its treatment: at diagnosis, during initial treatment (with HER2-targeted therapy and/or chemotherapy), after completion of initial treatment, and at one or more sites of metastasis. To create this model, she will analyze multiple regions within each tumor and also test circulating DNA that the tumor sometimes sheds into the blood. She will also examine the specific changes present in the cells that develop resistance to HER2-targeted therapy. A deeper understanding of how tumors evolve under the pressure of treatment will open new avenues to optimizing treatment delivery. Markers of treatment resistance may further allow us to personalize therapy choices, delivering extra therapy to those patients who need it and sparing others unnecessary toxicity.

Project title: "Breast cancer evolution and resistance in response to HER2-targeted therapy"
Institution: Stanford University
Award Program: Physician-Scientist
Sponsor(s) / Mentor(s): Christina N. Curtis, PhD, and Allison W. Kurian, MD
Cancer Type: Breast
Research Area: Evolution
Christopher A. Klebanoff, MD

A form of cancer immunotherapy termed adoptive T cell transfer (ACT) can induce long-lasting remissions in patients with advanced blood cancers. In this approach, T white blood cells specific for proteins found on the surface of cancer cells (antigens) are activated and expanded outside the immunosuppressive environment of a cancer patient's body before re-infusion as a therapy. Thus far, this promising form of cancer immunotherapy has failed to work in most patients with cancers arising from solid organs, the leading cause of cancer-related deaths in adults. Two critical gaps in knowledge limit the ability of ACT to be successfully applied to solid cancers: 1) understanding which antigens on the surface of cancer cells can be targeted by T cells that do not have the potential to cross-react and injure normal tissues, and 2) insight into what factor(s) limit the ability of transferred T cells to expand and persist following re-infusion into a patient. Dr. Klebanoff seeks to use a genetic engineering approach to simultaneously address both these issues. Success of these efforts would be a decisive step forward toward extending the ability of ACT to deliver potentially curative responses in patients with common cancers, including those arising from the breast, uterus, cervix and colon.

Project title: "Clinical development of next-generation T cell receptor (TCR)-based adoptive immunotherapies for the treatment of patients with common epithelial malignancies"
Institution: Memorial Sloan Kettering Cancer Center
Award Program: Clinical Investigator
Sponsor(s) / Mentor(s): Michel Sadelain, MD, PhD, and Larry Norton, MD
Cancer Type: Gynecological, Kidney and Bladder, Breast
Research Area: Immunotherapy
Philip A. Romero, PhD

Dr. Romero is a biomedical engineer whose expertise is in the area of microfluidics. He proposes to develop new technology that can be used to detect circulating tumor cells (CTCs) in the bloodstream. CTCs are cells that have detached from a solid primary tumor and entered into the bloodstream; they can go on to colonize distant sites and form metastases. Detecting CTCs is an enormous challenge, as the cells are present at an ultra-low abundance (1 out of billions of blood cells). His approach is to develop a highly specific system, a “DNA-based logic circuit,” to detect and profile CTCs, which could ultimately be applied for cancer diagnosis, prognosis indication, and measurement of a patient’s response to treatment.

Project title: "Digital circulating tumor cell detection using scalable molecular logic"
Institution: University of Wisconsin, Madison
Award Program: Innovator
Cancer Type: Breast, Colorectal, Lung, Prostate, Sarcoma
Research Area: Biomedical Engineering
Yichen Xu, PhD

Dr. Xu focuses on the estrogen receptor α (ERα), a nuclear hormone receptor that is mutated and hyperactivated in over 70% of breast cancers. Hormone therapy drugs, such as tamoxifen, which target classic ERα signaling are highly potent; however, many patients eventually develop drug resistance. His proposed research will address a previously unknown role of ERα in breast cancer progression and therapy resistance, and may identify a potential second-line therapy to treat breast cancer.

Project title: "Elucidating a non-classical role of ER in gene expression and breast cancer progression"
Institution: University of California, San Francisco
Award Program: Fellow
Sponsor(s) / Mentor(s): Davide Ruggero, PhD
Cancer Type: Breast
Research Area: RNA (RNA processing, miRNA and piRNA mechanisms, enzymatic RNAs, etc.)
Leeat Yankielowicz-Keren, PhD

Dr. Yankielowicz-Keren studies cellular changes in breast cancer, the second leading cause of cancer death in women in the U.S. Recently, a new multiplexed ion beam imaging (MIBI) technology has been introduced, which enables simultaneous imaging of dozens of proteins at a single cell level within a tissue section with high sensitivity. She is applying MIBI to study expression patterns of human breast cancer samples in the spatial context of the microenvironment and the interactions with the immune system. She aims to discover novel phenotypic and histologic features that predict progression from contained lesions to invasive disease.

Project title: "Studying the tumor immune microenvironment in breast cancer using a novel multiplexed imaging platform"
Institution: Stanford University
Award Program: Fellow
Sponsor(s) / Mentor(s): Michael R. Angelo, MD, PhD, and Edgar G. Engleman, PhD
Cancer Type: Breast
Research Area: Systems Biology
Yi Yin, PhD

Dr. Yin has developed single-cell assays that will be combined with statistical modeling to understand homologous recombination (HR). Cells use the process of HR to accurately repair harmful breaks that occur on both strands of DNA. Failure to correct such DNA damage can play a role in cancer initiation and progression. Dr. Yin aims to understand this critical mechanism to help guide treatment approaches for many cancer types.

Project title: "Global analysis of DNA break repair by single-cell sequencing"
Institution: University of California, Los Angeles
Award Program: Dale Frey Scientist
Cancer Type: Blood, Breast, Skin
Research Area: Chromosome and Telomere Biology
  • You can support our innovative researchers.