Lancaster Physician Spring 2021 - 9

SPRING 2021

A

s the No. 5 destination on U.S.
News & World Report's " Best
Places to Retire " list in 2020-21,
Lancaster County is home to
many people seeking to live out their golden
years. In fact, one out of every four county
residents is age 60 or older, according to
the county's Office of Aging.

Connor is leading Penn State College
of Medicine's involvement in the new
research project. Justin Lathia of Cleveland Clinic's Lerner Research Institute
and Jill Barnholtz-Sloan of Case Western
University School of Medicine are the principal investigators of the multi-institution
research team.

Unfortunately, advancing age brings an
increased risk for many health conditions.
One of the most concerning is glioblastoma, a common and deadly type of brain
cancer primarily diagnosed at older ages
(median age of 66 and 65 years, respectively), according to data from the Central
Brain Tumor Registry of the United States.
The median survival rate is 8 months, and
only 7.2 percent of patients are expected
to survive beyond five years.

RESEARCHERS ARE

But new research from Penn State College
of Medicine brings great hope. Researchers
are participating in a $10 million National
Cancer Institute-sponsored study to better
understand why males and females have different glioblastoma survival rates. Finding
an answer could lead to better and more
targeted therapies.

PARTICIPATING
IN A $10 MILLION
NATIONAL CANCER
INSTITUTESPONSORED
STUDY TO BETTER
UNDERSTAND
WHY MALES
AND FEMALES

STUDYING GLIOBLASTOMA AT
THE CELLULAR LEVEL
The study continues the longstanding
work of James Connor, PhD, distinguished
professor of neurosurgery, neural and behavioral sciences and pediatrics at the College
of Medicine. For most of his career, Connor
has studied how iron metabolism in brain
cells affects neurological disease. He began
investigating how iron regulation affects
glioblastoma outcomes after collaborators on
the current project found differences in the
activity of an iron-related transport protein
in male and female glioblastoma tumors.
" Cells cannot thrive if they lack adequate
iron; it's a necessary component of many
cellular processes, " Connor said. " We have
the unique expertise in our lab to further
explore how iron metabolism may play a
role in the survival difference between male
and female glioblastoma patients. "

HAVE DIFFERENT
GLIOBLASTOMA
SURVIVAL RATES.
Darya Nesterova, a medical and graduate
student at the College of Medicine, joined
Connor, Lathia, Barnholtz-Sloan, Vishal
Midya and other authors in a published
prior study demonstrating that differences
in the expression of the homeostatic iron
regulatory (HFE) gene can affect survival
outcomes in male and female glioblastoma
patients. They evaluated genetic data and
clinical outcomes of more than 450 patients
and found that in tumors with low HFE
expression, females had a 10-month survival
advantage. However, in tumors with high
HFE expression, there were poor survival
outcomes regardless of a patient's sex.

LANCASTER

9

PHYSICIAN

Connor said these results scratch the
surface of how iron metabolism in glioblastomas may affect survival. Researchers will
further explore how iron affects the complex
interactions between genetics and hormonal
factors in a tumor or its microenvironment,
and how that may affect survival outcomes
in male and female glioblastoma patients.

A TEAM APPROACH TO SEEKING
A CURE
" The goal of this new project is to better understand the biological and cellular
functions that drive sex differences in
glioblastoma formation and progression, "
said Dr. Robert Harbaugh, distinguished
professor and chair of the Department of
Neurosurgery at Penn State Health Milton
S. Hershey Medical Center.
To do so, the lab will rely on clinical
data collected by neurosurgeons Dr. Brad
Zacharia and Dr. Alireza Mansouri and neuro-oncologists Dr. Michael Glantz and Dr.
Dawit Aregawi with the Milton S. Hershey
Medical Center. " It's a prime example of
how our scientists, clinicians and patients
are working together to someday find a
cure for this deadly cancer, " Harbaugh said.
Todd Schell of the College of Medicine,
Dr. Joshua Rubin of Washington University
School of Medicine, and Michael Berens
of the Translational Genomics Research
Institute will also contribute to this research.
This project is supported by funds from
the National Institutes of Health (NIH).
The content is solely the responsibility of
the authors and does not necessarily represent the official views of the NIH. The
researchers declare no conflict of interest.



Lancaster Physician Spring 2021

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