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,
and that it modulates ERK signaling 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 a simplified view of the major signalling pathways relevant to cancer,
modified from Dr. Weinberg's review.
Mitogen-Activated Protein Kinase or MAPK
pathways are evolutionarily conserved kinase models
that link extracellular signals to the machinery
that controls 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 memory and 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 RTK's
can be activated by various mechanisms including mutation or overexpression.