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Hello. I'm Reiko Sugiura at the Laboratory of Molecular Pharmacogenomics.
Department of Pharmaceutical Sciences, Kindai University.
The title of my talk is:
A Novel Cancer Therapy to Stimulate Oncogenic ERK Signalling.
Recently our lab discovered a novel compound ACA-28,
which preferentially kills human melanoma cells.
This compound is very unique in that it modulates ERK signalling,
and induces ERK dependent apoptosis.
In this presentation, I'll give you an overview
of MAPK signalling and its relevance to cancer therapy.
Second I'll introduce our molecular and chemical genetic approach,
which led to the discovery of a novel ERK modulator, ACA-28,
and finally I would like to discuss
the medical impact of this new compound in cancer therapeutics.
Let's first review the MAPK signal transduction network - relevant to cancer.
This slide shows the simplified view of
the major signalling pathways relevant to cancer, modified from Dr. Weinberg's review.
Mitogen-activated protein kinase, or MAPK pathways,
are evolutionary conserved kinase modules that link
extracellular signals to the machinery that
control fundamental cellular processes such as growth,
proliferation, differentiation, migration, and apoptosis.
The Ras, Raf, MEK, ERK, MAPK pathway,
is one of the most studied of the mammalian MAPK pathways,
and has attracted intense research interest because of
its critical involvement in the regulation of cell proliferation and survival.
In normal cells, this signalling pathway,
especially Ras and the downstream ERK pathway,
regulates cellular functions such as proliferation and angiogenesis.
In tumor cells, a number of receptor tyrosine kinases or RTKs,
can be activated by various mechanisms, including mutation or over-expression.