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CANCER STEM CELLS AND
ONCOLOGY RESEARCH
11
th
International Conference on
Journal of Medical Oncology and Therapeutics
|
Volume 3
Elaine M Hurt et al., J Med Oncl Ther 2018, Volume 3
TARGETING NOTCH4 IN OVARIAN
CANCER RESULTS IN DECREASED
NUMBER OF CANCER STEM CELLS
AND INCREASED SURVIVAL WHEN
USED IN COMBINATION WITH
CISPLATIN IN PRE-CLINICAL
MODELS
Elaine M Hurt, Suneetha B Thomas, Jon Chesebrough, Tim
Hummer
and
Peter Pavlik
MedImmune LLC, USA
T
he Notch pathway plays a central role in the regulation of cellular
growth and differentiation. There are 4 known receptors and 5
ligands in this pathway. While all receptors have been shown to be
important in tumor biology, Notch4 continues to be implicated as a key
mediator of cancer stem cell (CSC) biology. CSC-targeted biologics are
an important part of a comprehensive oncology therapeutic strategy
due to the role of CSCs in tumorigenesis, therapeutic resistance and
patient relapse. Targeting this sub-population of cells is anticipated to
lead to more durable patient responses. We have developed a human
IgG1 antibody that targets the negative regulatory region of the Notch4
receptor, keeping it in an auto-inhibited state. We have determined
Notch4 is expressed by CSCs of many solid tumors and is increased by
cisplatin, a commonly used chemotherapy. Furthermore, uur anti-Notch4
antibody inhibits ovarian CSC growth
in vitro
and secondary tumor growth
in vivo
, consistent with depletion of CSCs. Combination of our anti-
Notch4 antibody with cisplatin in ovarian tumor models demonstrates
a more durable response than cisplatin alone, as expected with a CSC-
combination therapeutic approach. Overall targeting Notch4 with an
inhibitory antibody demonstrates superior ability, as compared with other
Notch pathway inhibitors, to inhibit CSCs in preclinical models.
Elaine M Hurt received her PhD in Biochemistry,
Molecular Biology and Biophysics from the Uni-
versity of Minnesota in 1999 where she studied
estrogen receptor signaling cascades. She did
her post-doctoral studies at the National Insti-
tutes of Health in the laboratory of Dr. Louis
Staudt elucidating the molecular mechanisms
governing therapeutic responses in lymphoma
and multiple myeloma patients. In 2010, She-
joined MedImmune to lead their cancer stem
cell group. Prior to joining MedImmune, She
was a Staff Scientist at the National Cancer In-
stitute, where she focused primarily on identify-
ing and targeting prostate cancer stem cells. In
2014, She became Adjunct Associate Professor
in the Department of Biochemistry and Molecu-
lar Biology at the University of Maryland. She is
the co-inventor on several patents, has been an
invited speaker at numerous conferences, and
has published over 50 scientific articles.
elaine.hurt@yahoo.comBIOGRAPHY