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Printable Handouts
Navigable Slide Index
- Introduction
- RNAi will allow designing novel cancer therapies
- Establishment of cancer - a multistep phenomenon
- Proliferation-differentiation balance in cells
- Regulation of cell proliferation and differentiation
- Establishment of cancer - programmed cell death
- Cancer protection pathways in normal cells
- Programed cell death in damaged cells
- The importance of invasiveness in cancer
- Loss of cell migration control in cancer
- VEGF involvement in tumor invasiveness
- Tumor suppressors and oncogenes
- Inactivation of genes that protect the genome
- Essential genes are modified in oncogenesis
- Characterization of regulation genes in normal cell
- Loss-of-function assays
- The need of a tool to block each gene individually
- Attempts to create tools by antisense strategy
- RNA interference in animals
- RNA interference use a distinct cellular pathway
- RNA interference with siRNAs
- siRNA as a tool to explore genes fuction
- High throughput functional analysis
- Pionneer studies using siRNA and shRNA
- Are RNAi pathways deregulated in cancer?
- RNA interference uses the miRNA pathway
- Pionneer sudies in miRNA cell control involvement
- Involvement of miRNA pathways in cancer
- miRNAs are potential tumor suppressors
- miRNAs can also act as oncogenes
- Involvement of other RNAi pathways in cancer
- RNA interference can affect transcription
- RNAi and novel cancer therapies
- De-regulation of oncogenes and tumor suppresor
- Involvement of genes in cancer maintenance
- Induction of cell death in p53 siRNA mutant cells
- Potential targets
- Essential genes for cancer establishment
- Inhibition of cell control genes
- siRNAs discriminate wild-type and p53 mutants (1)
- siRNAs discriminate wild-type and p53 mutants (2)
- Specificity of inhibition
- Essential questions need to be resolved
- Plasmidic shRNA
- Plasmidic shRNA expression vectors
- Plasmidic shRNA- advantages and disadvantages
- Synthetic siRNAs
- Synthetic siRNA- advantages and disadvantages
- Problems associated with synthetic siRNA use
- RNAi in vivo: two hurdles to overcome?
- Is stabilization of siRNA required?
- Available vectorization procedures
- Is vectorization of siRNA in vivo required?
- Tumor growth inhibition by VEGF silencing
- The question of delivering siRNA to the right place
- Achieving long term inhibition with synthetic siRNA
- Synthetic siRNA- potential uses
- Fighting hypermutation phenotype
- RNA interference is a potentially powerful tool
- Future cancer treatments
Topics Covered
- Cancer overview
- RNA interference to understand cancer
- Natural short RNAs in cancer
- RNA interference to fight cancer
Links
Series:
Categories:
Therapeutic Areas:
Talk Citation
Harel-Bellan, A. (2016, October 13). RNA interference and cancer: a revolution? [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 22, 2024, from https://doi.org/10.69645/NCJA3720.Export Citation (RIS)
Publication History
Financial Disclosures
- Dr. Annick Harel-Bellan has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
A selection of talks on Genetics & Epigenetics
Transcript
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0:00
Because it is so efficient,
RNA interference represents a true revolution in many domains,
and it is also true for cancer.
0:11
I am confident that RNA interference will
facilitate the design of new cancer therapies and this is for two reasons.
First, because it allows to explore
all the pathways that are deregulated in cancer cells,
and thus discover new targets.
And second, because it might be used to inhibit
specifically noxious genes that are required for cancer cell survival.
0:40
For example, this slide summarizes what we know on colon cancer.
To go from a normal tissue to a cancer able
to invade other tissues and create metastasis takes many different steps,
and involves a number of various genes and pathways that more or less control cell fate.
And this does not take into account the fact that cancers are heterogeneous,
and even for a given cancer type there is
a very high level of variability between patients.
Let's review very briefly what we know about oncogenesis.
It all begins with the regulation of
the balance between cell proliferation and differentiation.
For example, in the skin the population of precursor cells proliferates,
1:21
which means that they go through the mitotic cell cycle,
the sequential series of events during which
each individual cell duplicates all its components,
including the genetic material,
and then divides and gives birth to two identical daughter cells.
The skin cell progresses from the bottom to the top in this picture.
At some point, the precursor cells exit from
the mitotic cycle and enter the terminal differentiation program.
And at the top what we find are fully differentiated cells.
In most tissues the cells have to exit from the mitotic cycle to
differentiate, and the number of cells that proliferate and
differentiate is strictly balanced.
Cell proliferation is controlled by negative signals or repressors that are switched off,