Experts at Auburn University HCOP discover highly potent and selective anticancer treatment
For most academic scientists conducting biomedical research, the possibility of advancing a new medicine from the lab to the clinic is, at best, an aspiration. Despite the odds, Gary Piazza and his research team in the Auburn University Harrison College of Pharmacy (HCOP) have discovered a highly potent and selective anticancer treatment and are collaborating with investigators at the University of Alabama-Birmingham (UAB) O’Neal Comprehensive Cancer Center to advance a new drug candidate to clinical trials for patients with the most fatal of cancers.
Piazza joined HCOP in 2021 as the W.W. Walker Professor and head of the Department of Drug Discovery and Development. A highly respected cancer investigator, Piazza came to Auburn as a UAB graduate with more than 35 years of research experience, including 10 years as a professor at the University of South Alabama Mitchell Cancer Institute in Mobile and 10 years as a principal scientist with Southern Research in Birmingham.
Along with his administrative responsibilities, Piazza continues his groundbreaking research as director of the newly created Cancer Research Center at HCOP.
A team of scientists who started to collaborate while at Southern Research also made the move from MCI to Auburn, including Xi Chen, a medicinal chemist; Adam Keeton, a cancer biologist; Yulia Maxuitenko, a pharmacologist; and Kristy Berry, a lab manager with expertise in mouse tumor models.
“We share a common interest in cancer research but have very different skill sets,” said Piazza. “Having a multidisciplinary team with diverse scientific expertise has allowed us to solve many technical problems as we seek to advance our experimental drugs to the clinic.”
Learn more about this research
Such work underway by Piazza and the Cancer Research Center is among several projects at Auburn aimed at discovering better treatments and answers in a wide range of focus in the fight against cancer. In recognition of May being National Cancer Research Month, the following is a closer look at some of those projects:
MULTIDISCIPLINARY FACULTY TEAM STUDY LINK BETWEEN COLORECTAL CANCER, OBESITY
Virus research team
Mike Greene, an associate professor of nutrition, and Elizabeth Lipke, the Mary and John H. Sanders Professor of chemical engineering, are collaborating to study the link between colorectal cancer and obesity.
There is an established link between colorectal cancer diagnosis and obesity, but understanding why that link is present and how best to treat such a dual diagnosis is still not fully understood by doctors and researchers. Thanks to a nearly $2.5 million R01 research award from the National Institutes of Health (NIH), an interdisciplinary team from three universities led by Elizabeth Lipke, the Mary and John H. Sanders Professor in the Department of Chemical Engineering in the Samuel Ginn College of Engineering, and Mike Greene, an associate professor of nutrition in the Department of Nutritional Sciences in the College of Human Sciences, will examine this link and aim to understand how best to treat these patients to improve clinical outcomes.
Colorectal cancer is the third-most common non-skin-related cancer and the third-leading cause of cancer-related mortality in the United States. Obesity is linked to an increased risk of death from colorectal cancer. Although overall colorectal cancer incidence rates declined from 1991-2011, they have risen recently in younger age groups and remain high in states with a high incidence of obesity.
“This is a very collaborative approach working both on the engineering side and on the biological side to make paired models of colorectal cancer,” Lipke said.
Lipke, whose expertise lies in tissue engineering, and Greene, whose research focuses on metabolic diseases, are co-principal investigators on the project.
Learn about their research
COLLEGE OF SCIENCES AND MATHEMATICS ASSISTANT PROFESSOR INVESTIGATING CANCER-ALTERING REOVIRUS
Mike Greene and Elizabeth Lipke
The research team out of the College of Sciences and Mathematics investigating cancer-causing Reovirus includes Diego Gomes, Rafael Bernardi and Priscila Gomes, with Bernardi holding a replica of a virtual Reovirus like the one featured in their research project.
Almost 20 million new cancer cases were detected in 2020, and about 10 million people died globally from this disease that year, according to the National Institutes of Health. In the Department of Physics at Auburn, a team of scientists are working to make breakthroughs in understanding more about the Reovirus, which offers promising therapy options to destroy cancer cells.
Think of a Reovirus as a virus that can infect humans, animals and even plants.
However, it also can bind or attach itself to cancer cells, providing a means to infect and destroy the tumor.
The team includes Rafael C. Bernardi, assistant professor, and postdoctoral researchers Diego and Priscila Gomes. They recently published the results of their study in the prestigious journal “Proceedings of the National Academy of Sciences,” titled, “Deciphering molecular mechanisms stabilizing the reovirus-binding complex.”
Learn about this research
VETERINARY MEDICINE’S MERNER STUDIES GENETIC CANCER RISK FACTORS IN AFRICAN AMERICAN COMMUNITY
A team of researchers in Auburn’s College of Veterinary Medicine is working to identify and study genetic factors associated with hereditary breast cancer in the African American community. According to Nancy Merner, team leader and assistant professor of pathobiology, it is an area where further research has been badly needed.
Nancy Merner
Nancy Merner, assistant professor of pathobiology, is leading a team of researchers to study genetic cancer risk factors in the African American community.
“African American women have higher breast cancer incidence rates before the age of 40 than other ethnic groups in the United States,” Merner explained. “They are also more likely to be diagnosed with triple-negative breast cancer, a more aggressive subtype with a poor prognosis. These facts, coupled with reports of African American males having higher breast and prostate cancer frequencies than other ethnicities, suggest that hereditary factors are involved.”
Despite the higher incidence of these cancers in the African American community, Merner said there have been an insufficient number of studies to determine the causes. So, she and her research group have sought out families with a history of such cancers while traveling the state, spreading cancer awareness in a pink bus called “the Gene Machine” and — during the pandemic — using online resources.
Merner’s team conducts two similar breast cancer genetic studies, each focused on a different species — humans and canines. Due to the genetic similarities of the two species, when studied in parallel, disease gene discovery efforts that apply to both species are greatly enhanced. Purebred dogs with canine mammary tumors (CMTs) represent very practical models for human breast cancer; however, as is the case with hereditary breast cancer studies in the African American community, the genetics of hereditary CMTs is incredibly understudied.
Aligned with the college’s One Health focus, Merner’s canine model of hereditary breast cancer will provide a better understanding of inherited breast cancer risk in both dogs and humans and, in turn, better understanding of increased disease frequency affecting African Americans.
Learn about Merner’s research
VETERINARY MEDICINE RESEARCHER DEVELOPING NOVEL IMMUNOTHERAPIES TO TREAT CANINE CANCER WITH POTENTIAL TO IMPROVE HUMAN CANCER THERAPEUTICS
Dr. Maninder Sandey
Dr. Maninder Sandey’s research focuses on developing novel immunotherapies to treat canine cancer.
Throughout their careers, veterinarians care for many canine cancer patients and witness the devastating effects of this disease. Dr. Maninder Sandey is among these ranks. His experience treating dogs with cancer has turned into a determination to learn more about how cancer works at the molecular level while finding better ways to treat it that could help both dogs and people.
Cancer is one of the most common causes of death in humans and in the geriatric dog population. The mean survival time and overall survival for canine cancer patients are alarmingly low. However, naturally occurring cancers in dogs share many similarities with human cancer.
“By studying how treatments work in canine cancer patients, we can learn valuable information that can benefit both people and dogs,” said Sandey, associate professor of pathology in the College of Veterinary Medicine’s Department of Pathobiology. “Thus, our approach will provide dogs with cutting-edge immune therapies, while ensuring that people have access to treatments that are more likely to succeed.”
After earning his Doctorate in Veterinary Medicine, Sandey decided to pursue a doctorate in biomedical sciences from Auburn. Coupled with his experience caring for canine cancer patients, his doctoral research experience has transformed into a dedication to developing new immunotherapies that could completely change the way cancer is fought in dogs by utilizing proven human cancer treatment methods.
Read more about Sandey’s work in treating canine cancer.
HARRISON COLLEGE OF PHARMACY RESEARCHERS SEEK ANSWERS TO BREAST CANCER, TREATMENT WITH FOUNDATION SUPPORT
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Rusty Arnold
Rusty Arnold
Alexei Kisselev
Alexei Kisselev
The Breast Cancer Research Foundation of Alabama funds various research projects across the state. At Auburn, the organization has recently supported the work of two professors in the Harrison College of Pharmacy.
For his study, “Highly Active Liposomal Formulation of Proteasome Inhibitor Carfilzomib for the Treatment of TNBC,” Alexei Kisselev, an associate professor in the Department of Drug Discovery and Development, is seeking to develop a novel treatment for the most-deadly form of breast cancer, triple-negative breast cancer (TNBC), which is characterized by early age of onset, early relapse and aggressive growth.
TNBC disproportionately affects African American women and does not respond to common agents used to treat the majority of breast cancers.
“We are working with a class of drugs called proteasome inhibitors, which are approved for the treatment of multiple myeloma, a bone marrow cancer,” said Kisselev. “These drugs kill cells derived from TNBCs in a petri dish at lower concentrations than any other FDA-approved TNBC treatment.
“Unfortunately, this activity has not yet translated to clinical activity because of insufficient tumor penetration by these compounds and due to their toxicity to normal tissues. To solve these problems, we developed a nano-formulation of one of these agents, carfilzomib (Kyprolis), in which it is packed in lipid droplets called liposomes that penetrate tumors but not normal tissues.”
In the preliminary experiment, Kisselev’s team found that carfilzomib blocked growth of TNBC tumors in mice.
By using the foundation’s grant, the team is studying the effects of this formulation on human tumors growing in immunodeficient mice, with the goal of identifying biological markers that will help them to select patients more likely to respond to this drug.
“We will use data obtained with this award to support our applications for federal funding, which we will use to conduct testing in additional patient-derived models, including combination with agents that currently used for the treatment of TNBC, and studies to better understand why TNBC is so sensitive to proteasome inhibitors,” said Kisselev. “Our ultimate goal is to conduct clinical trials of the formulation in human patients.”
Members of Kisselev’s team include his colleagues in the Department of Drug Discovery and Development Professor Rusty Arnold, Associate Research Professor Yulia Maxuitenko and Assistant Professor Amit Mitra, as well as David Redden from the Edward Via College of Osteopathic Medicine in Auburn.
Arnold’s research project funded by the Breast Cancer Research Foundation of Alabama, “Carrier-Free Quercetin Nanoparticles for Overcoming Breast Cancer Drug Resistance,” is a collaboration with Yuping Bao, an associate professor of chemical and biological engineering at the University of Alabama.
The pair seek to find the underlying biological causes and novel cancer treatments to overcome multidrug resistance (MDR) — the phenomenon that cancer cells stop responding to chemotherapeutic drugs during treatment.
Arnold said there has been an increased understanding of drug resistance over the last decade, but without knowing the underlying biological causes and novel treatments, MDR remains responsible for most of the breast cancer treatment failures and deaths. MDR is also believed to be directly associated with breast cancer metastasis and relapse.
An answer may lie in quercetin, one of the major natural flavonoids from fruits and vegetables, as Arnold said it has demonstrated great pharmacological potential in overcoming MDR. However, the clinical applications of quercetin have been limited.
“In this project, we propose to develop quercetin-Fe complex nanoparticles to address those limitations,” he said. “Subsequently, we will determine their effectiveness and underlying mechanisms in overcoming MDR using an aggressive, triple-negative, drug-resistant breast cancer cell line.”
The team is theorizing that nanoparticle formation can increase the stability, improve the aqueous solubility and overcome fast clearance of quercetin. The nanoparticle formation also offers the potential for tumor targeting.
“The key innovation of our project is carrier-free nanoparticle formation, which eliminates the dependence on carrier matrix for quercetin encapsulation and drug release in typical nanocarriers,” said Arnold. “Our overall goal is to develop a carrier-free nanoparticle system based on natural products to reverse MDR of breast cancer cells and improve existing anticancer activity.”