Research Progress Report

Indiana University School of Medicine
(Tuesday, December 3, 2019)
Indiana University School of Medicine reports on the progress at the Vera Bradley Foundation Center for Breast Cancer Research

INDIANAPOLIS –Some of the research happening at the ​Vera Bradley Foundation Center for Breast Cancer Research

Prevention and Early Detection

Preventing breast cancer starts with understanding how healthy cells become cancerous. Researchers in the Vera Bradley Foundation Center for Breast Cancer Research are investigating which cells change and what influences the changes. This information will help women at high-risk for breast cancer make informed decisions about prevention choices.

Hari Nakshatri, PhD and his laboratory team are investigating how genetic ancestry impacts the biology of the normal breast and susceptibility for developing breast cancer. He and Anna Maria Storniolo, MD, have recently received a prestigious grant from the Chan Zuckerberg Foundation to further this work. Their goal is to map the genes of 75 healthy tissue samples from women of different genetic ancestries to learn the types of cells that are present in the breast, how cell composition differs between women of different genetic ancestry, and, eventually, how to understand cellular changes that are age related.

Jaeyeon Kim, PhD, and Vera Bradley Foundation Scholar Olga Kim, MD, PhD,
are examining the role hormones play in breast cancer development. Their research reveals that a hormone produced from the ovary may play a crucial role in the development of breast cancer in women with the BRCA1 and BRCA2 mutations. Carrying the gene increases the risk of breast cancer, but not every carrier will get breast cancer. Understanding the process that links the hormone to the development of a breast tumor may lead to accurate predictions about who will likely develop cancer.

Of the 5,000 healthy samples of breast tissue housed at the Vera Bradley Foundation Center, 19 of the women who donated their tissue went on to develop breast cancer and have donated their tumor tissue as well. This is allowing N atascia Marino, PhD, to compare each set of tissue. Already, differences have been detected that may identify the early pathways to breast cancer development.

New Drug Development

Many of the laboratory researchers who work in the Vera Bradley Foundation Center for Breast Cancer Research focus on developing new drugs to treat aggressive breast cancers. Once their laboratory work is completed, the FDA determines which drugs will move to the clinic for testing safety and effectiveness with patients. If successful, these new drugs may become breast cancer treatments of the future.

Xiongbin Lu, PhD, and Xinna Zhang, PhD, previously discovered a key breast cancer treatment target in tumors and have now successfully treated it with a novelnanoparticle-delivered drug that Dr. Lu developed. Their research was tested in lab animals and demonstrated a profound reduction of tumor growth when it supplemented standard treatment. Their goal now is to test this in the clinic. If successful there, 11-18% of all breast cancer patients stand to benefit.

Charlie Hao, MD, PhD,
identified a way that cancers essentially throw out the trash, which most likely includes proteins that control their growth, thus allowing the tumors to thrive. He and Anita Bellail, PhD, discovered that a particular protein that drives cancer growth and have now developed a potent inhibitor (SMIC1007) that turns off this protein. In the laboratory, SMIC1007 inhibits the growth of multiple cancers including breast, colorectal, and lung. Laboratory research is moving rapidly to the clinic, and he is anticipating that the first clinical trial with this drug will be within three years.

Triple Negative Breast Cancer

Triple-negative breast cancer (TNBC) is an especially aggressive type of breast cancer with a high likelihood of recurring and spreading. It often does not respond to treatment. IU researchers in the Vera Bradley Foundation for Breast Cancer Research Laboratories are developing personalized treatments with the goal of developing effective treatments for women with this disease.

Kathy Miller, MD, designed the first clinical trial combining two new drugs that genetically target metastatic triple negative disease. It is just concluding and this treatment has been effective for some of the women participants. Milan Radovich, PhD, who developed the laboratory evidence to pursue the clinical testing, is now studying biopsy samples from the women who enrolled in Dr. Miller’s study to understand why it worked for some women but not for all. Promising information is being revealed. Clinical research will continue with a refined approach that further individualizes treatment for women with metastatic TNBC disease.

Patients with more aggressive triple negative disease receive chemotherapy before surgery, and while some tumors shrink away to nothing, others do not. Bryan Schneider, MD, is studying these remaining tumors with two goals: The first goal is to understand why the best drugs did not work, and what causes those tumors to be resistant. The second goal is to develop a more sophisticated genetic analysis of TNBC tumors and refine treatments with more highly targeted drugs. One discovery of the trial is that resistant tumors fall into several big groups that require individualized approaches. Dr. Schneider has begun developing his next clinical trial.

Xiongbin Lu, PhD, is using nanotechnology to deliver a cancer-killing drug into the genetic core of triple negative breast cancer cells. Described as a “nano-bomb,” it targets TNBC cells by connecting to a gene near a major cancer-causing gene in these cells. Once delivered, the bomb grows to 100 times its normal size and, through a controlled release, kills only the cancerous cell, leaving the healthy cells alive. Lu and a collaborator at the University of Maryland have patented this nanotechnology approach, which also has potential implications in other cancers including ovarian, lung and colorectal cancer. This research is still in laboratory testing.

Chunhai Hao, MD, PhD, has also uncovered another way that tumors control their signaling and growth. This new target holds promise for the treatment of triple negative breast cancers. He has taken this a step further and identified drugs that block this pathway and is now studying them in the laboratory as a possible treatment.

Aggressive and Recurrent Disease

Kathy Miller, MD is taking a Vera Bradley Foundation Center finding and leading a national clinical trial to block an enzyme that is expressedwhen cells become resistant to standard chemotherapies. The trial adds a commonly used ulcer drug to inhibit the enzyme with standard chemotherapy. Her hope is that with the addition of the new drug that the chemotherapy continues to be an effective cancer inhibitor.

Claire Walczak, PhD, hasrecently discovered that a key protein present in cancer cell division that mayenhance their own survival and proliferation. Her laboratory’s expertise in biochemistry and high-resolution imaging is being utilized to discover how to inhibit this protein activity. Their goal is to block this protein in breast cancer cells to determine if this strategy will stop the cells from reproducing.

Healthy Survivorship

For women with breast cancer, treatment steals precious time from their lives and treatment can lead to long-term health issues. Funding from the Vera Bradley Foundation for Breast Cancer is helping IU researchers make therapy more effective and less toxic.

Tarah Ballinger, MD, is studying metastatic estrogen receptor (ER) positive patients to determine if muscle mass contributes to the effectiveness of treatments. Muscle is a large, active organ that influences the physical function, quality of life, metabolism and inflammation in the body. Dr. Ballinger and her colleagues want to learn if the muscle mass of patients, who are taking aromatase inhibitors (the most commonly prescribed drug in breast cancer), correlates to treatment outcomes. In addition to survival outcomes, she is also including quality of life, pain, and fatigue in her analysis. Results will help clinicians optimize drug dosing and potentially explain why effective drugs stop working for some patients. She is hopeful that the research outcome will be a prescription for state-of-the-art personalized resistance training programs and innovative non-exertional approaches to muscle development for women receiving treatment.

Bryan Schneider, MD, has spent his career studying why women, based on their genetics, respond differently to the same cancer medications, often with debilitating or life-threatening side effects. He has recently received a new grant to work with African American women diagnosed with breast cancer to develop information to explain their increased risk for neuropathy from taxane drugs and engage in shared decision-making with their oncologists to reduce this harmful side effect.

About Indiana University School of Medicine IU School of Medicine is the largest medical school in the U.S. and is annually ranked among the top medical schools in the nation by U.S. News & World Report. The school offers high-quality medical education, access to leading medical research and rich campus life in nine Indiana cities, including rural and urban locations consistently recognized for livability.

Source: Indiana University School of Medicine