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Printable Handouts
Navigable Slide Index
- Introduction
- ACA-28 discovery
- Lecture outline
- Major signalling pathways relevant to cancer
- Hyper-activated MAPK signalling leads to cancer
- The ERK MAPK pathway and cancer
- Raf/MEK/ERK signalling cascade inhibitors
- Limitations of MAPK targeted cancer therapies
- Fission yeast as a model organism
- Common drug targets in yeast and humans
- Evolutionary conservation of the MAPK pathway
- Regulators of the MAPK signalling pathway (1)
- Negative regulators of the MAPK pathway
- Rho/PKC and Ca2+ activate MAPK signalling
- Regulators of the MAPK signalling pathway (2)
- Chemical genomic screening of ACA derivatives
- The development of malignant melanoma
- Current chemotherapy for melanoma
- ACA-28 as a modulator of MAPK signalling
- Comparison of ACA-28 and dacarbazine
- ACA-28 preferentially kills melanoma cells
- Molecular basis of ACA-28 sensitivity
- ACA-28 reduces HER2 transformed cell viability
- ACA-28 effects on melanoma cells
- ACA-28 effects on HER2 transformed cells
- MEK inhinitor attenuates ACA-28 activitry
- Killing cancer cells via MAPK signalling (1)
- Inducing ERK-dependent apoptosis
- ACA-28 effects on RasG12V transformed cells
- Killing cancer cells via MAPK signalling (2)
- Acknowledgements
Topics Covered
- MAPK signalling and its relevance to cancer therapy
- The discovery of ACA-28
- The use of yeast within drug discovery
- Effect of ACA-28 on the apoptosis of cancer cells
- Implications of ACA-28 in cancer therapeutics
Links
Series:
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Therapeutic Areas:
Talk Citation
Sugiura, R. (2018, October 31). A novel cancer therapy to stimulate oncogenic ERK signalling [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved November 9, 2024, from https://doi.org/10.69645/VWGI4904.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Reiko Sugiura has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
Other Talks in the Series: Periodic Reports: Advances in Clinical Interventions and Research Platforms
Transcript
Please wait while the transcript is being prepared...
0:00
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.
0:20
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.
0:40
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.
1:08
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.