Molecular Biology seminar about pancreatic ductal adenocarcinoma (PDAC) and how the inhibition of the enzyme that is overexpressed in this case: Aurora Kinase, can help suppress this disease. All of this through the inhibitor gen MLN8237..

1. Isabella Peláez Corrales
Third semester
Universidad Pontificia Bolivariana

2. Introduction
Pancreatic Cancer
01
5-year survival
rate of 9%
02
Limited options of
appropriate
chemotherapy drugs
03 04
Overexpression:
unchecked cell
growth
Pancreatic Ductal Adenocarcinoma (PDAC): lethal disease
Aurora Kinase
(AURKA)

3. Introduction
Specific AURKA inhibitor
Phase III evaluation
Anticancer activity
Inhibition of proliferation
and migration
Introduction
MLN8237
Apyrimidobenzazepines,
Alisertib
Compounds with
BENZENE fused to
AZEPINES

4. Objective of the study
Evaluate how Aurora kinase a inhibitor MLN8237 suppresses
pancreatic cancer growth

5. Methods
Transwell assay and
western blotting
Reaction between antigen and antibody
2 basic principles:
-Protein electrophoresis
-Indirect Elisa
In this case it was used to evaluate the
expression levels of AURKA (antiboides)
using a normal pancreas and PDAC
tissues
Cell lines and cell culture
Process by which cells are grown in
favorable artificial environment
In this case it was used to determine
if MLN8237 affected pancreatic
cancer cell proliferation tested in
four different cell lines:
-ASPC-1
-BxPC-3
-Mia Paca-2
-PANC-1

6. Methods
Immunohistochemistry
staining
Detects antigens from a cell tissue.
Principle: antibodies bind
specifically to antigens in biological
tissue.
In this case it was used to confirm
the increased expression of AURKA
in cancer tissue from human PDAC
and pancreatic cancer animal model
(p53/LSL/Pdx-Cre).
Mouse orthotopic and genetic
pancreatic cancer models
Orthopic pancreatic cancer models:
-Six-week-old male nude mice
-Mia Paca-2
-MLN8237
-Gemcitabine hydrochloride
Genetic pancreatic cancer models:
-p53/LSL/Pdx-Cre mice
-MLN8237
-gEMCITABINE
-Saline (control)

7. Results

8. Results

9. Author Statement The authors of the
article…
Xie et al “Imatinib, a PDGF receptor (platelet-derived growth factor receptor)
inhibitor, significantly enhanced the anti-proliferative effect, G2/M
cell cycle rest, and apoptosis of Aurora B kinase-specific inhibitor
and a pan Aurora kinase inhibitor”.
Neel et al “This data is consistent with recent studies showing that MLN8237
inhibits tumor growth in the mouse patient-derived xenograft
models”.
Yin et al “Recently, MLN8237 demonstrated synergistic efficacy with a PD-
L1 antibody for the treatment of breast cancer cell 4 T1 xenografts”.
Discussion

10. Conclusion
The variety of molecular biology tools allows us to understand how a
disease such as cancer develops. With this, it is much easier for
scientists to find a solution that can suppress the function of the
enzyme/protein causing cell proliferation.
The molecular biology tools allow scientists to have evidence in order
to know if the experiment that they are trying is having positive or
negative results. Through this, they can seek other options and start
thinking about further ideas.