discovering which protein is altered in one type of cancer examining cancer cells treated with these...
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Discovering which protein is altered in one type of cancer
Examining cancer cells treated with these chemicals to see their effects
Analyzing all of the data to determine which chemicals are most promising
Steps in the discovery of new cancer treatments
Making analogs of each chemical, & measuring their potencies
Testing each potential new treatment in a clinical trial
Sharing findings with the scientific community & the general public
Synthesizing large batches of each promising chemical
Synthesizing small amounts of thousands of different chemicals
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Please take a moment to discuss with your neighbor how cancer has impacted those around you.
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All of the chromosomes in a non-cancerous cell
What has changed about the DNA in the cancer cell, that may have led to the disease?
Chromosomes #9 & #22 in a non-cancerous cell
Chromosomes #9 & #22 in a “CML” cancer cell
All of the chromosomes in a “CML” cancer cell
9 229 22
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DNA
Gene
Cell
ChromosomeNucleus
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The Basic Structure of DNA
Base pairs
Sugar Phosphate Backbone
Adenine Thymine
Guanine Cytosine
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A translocation is when two chromosomes swap their ends
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922
The translocation present in CML cancer patients
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The genes encoding Bcr & Abl in a non-cancerous cell:
If a translocation occurs between chromosomes 9 & 22...
The proteins Bcr & Abl in a non-cancerous cell:
Draw what the Bcr-Abl fusion proteinwould look like
in a “CML” cancer cell.
Draw what the Bcr & Abl genes would look like
in a “CML” cancer cell.
Bcr Abl
Chromosome 9 Chromosome 22
Bcr
Abl
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Normal cells with no translocation:
CML cancer cells with a translocation:
BcrProtein
AblProtein
Chromosome 9 Chromosome 22
Bcr
Abl
BcrAbl
Bcr-Abl Fusion ProteinTranslocated Chromosomes 9 & 22
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Discovering which protein is altered in one type of cancer
Examining cancer cells treated with these chemicals to see their effects
Analyzing all of the data to determine which chemicals are most promising
Steps in the discovery of new cancer treatments
Making analogs of each chemical, & measuring their potencies
Testing each potential new treatment in a clinical trial
Sharing findings with the scientific community & the general public
Synthesizing large batches of each promising chemical
Synthesizing small amounts of thousands of different chemicals
![Page 11: Discovering which protein is altered in one type of cancer Examining cancer cells treated with these chemicals to see their effects Analyzing all of the](https://reader036.vdocuments.us/reader036/viewer/2022062717/56649e495503460f94b3cc62/html5/thumbnails/11.jpg)
Discovering which protein is altered in one type of cancer
Examining cancer cells treated with these chemicals to see their effects
Analyzing all of the data to determine which chemicals are most promising
Steps in the discovery of new cancer treatments
Making analogs of each chemical, & measuring their potencies
Testing each potential new treatment in a clinical trial
Sharing findings with the scientific community & the general public
Synthesizing large batches of each promising chemical
Synthesizing small amounts of thousands of different chemicals
![Page 12: Discovering which protein is altered in one type of cancer Examining cancer cells treated with these chemicals to see their effects Analyzing all of the](https://reader036.vdocuments.us/reader036/viewer/2022062717/56649e495503460f94b3cc62/html5/thumbnails/12.jpg)
negative control
Background for this experiment: Cancer cell samples have been treated with a negative control, a positive control, and a promising new anti-cancer drug “Chemical A.” The DNA in the cells has been stained, so that each nucleus appears as a bright spot. Photographs of the cells were taken and are shown here.
positive controlpromising new anti-cancer drug
“Chemical A”
1) What does it mean about what has happened to the cancer cells, when there are lots of bright dots in an image (versus very few bright dots)?
2) How and why would cancer researchers conclude from these photos that “Chemical A” is indeed a promising new anti-cancer drug?
3) What do you think might have been used as a positive control and a negative control in this experiment? Explain your answer.
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a negative control a positive control
a promising new anti-cancer drug
“Chemical A”
Many cancer cells are alive.
Few cancer cells are alive.
Few cancer cells are alive.
Photos of cancer cells treated with:
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Discovering which protein is altered in one type of cancer
Examining cancer cells treated with these chemicals to see their effects
Analyzing all of the data to determine which chemicals are most promising
Steps in the discovery of new cancer treatments
Making analogs of each chemical, & measuring their potencies
Testing each potential new treatment in a clinical trial
Sharing findings with the scientific community & the general public
Synthesizing large batches of each promising chemical
Synthesizing small amounts of thousands of different chemicals
![Page 15: Discovering which protein is altered in one type of cancer Examining cancer cells treated with these chemicals to see their effects Analyzing all of the](https://reader036.vdocuments.us/reader036/viewer/2022062717/56649e495503460f94b3cc62/html5/thumbnails/15.jpg)
Initial compound
Reverse the atoms =improved potency
Remove lower region =improved solubilitybut lower potency
Add nitrogen =improved stabilitybut lower potency
or or
Add chlorine =even better potency!
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Which of these three chemical compounds is the most potent?
concentration of the chemical compound (μM)
Activity level of the target of this chemical compound (%)
Original CompoundAnalog XAnalog Y
This graph is called a “dose response curve,” and it shows the amount that a chemical compound inhibits the activity of the cell/protein that it targets.
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The chemical compound “Gleevec” binds to & inhibits the Bcr-Abl fusion protein
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Discovering which protein is altered in one type of cancer
Examining cancer cells treated with these chemicals to see their effects
Analyzing all of the data to determine which chemicals are most promising
Steps in the discovery of new cancer treatments
Making analogs of each chemical, & measuring their potencies
Testing each potential new treatment in a clinical trial
Sharing findings with the scientific community & the general public
Synthesizing large batches of each promising chemical
Synthesizing small amounts of thousands of different chemicals
![Page 19: Discovering which protein is altered in one type of cancer Examining cancer cells treated with these chemicals to see their effects Analyzing all of the](https://reader036.vdocuments.us/reader036/viewer/2022062717/56649e495503460f94b3cc62/html5/thumbnails/19.jpg)
A clinical trial shows us how well patients respond to a new treatment
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Discovering which protein is altered in one type of cancer
Examining cancer cells treated with these chemicals to see their effects
Analyzing all of the data to determine which chemicals are most promising
Steps in the discovery of new cancer treatments
Making analogs of each chemical, & measuring their potencies
Testing each potential new treatment in a clinical trial
Sharing findings with the scientific community & the general public
Synthesizing large batches of each promising chemical
Synthesizing small amounts of thousands of different chemicals
![Page 21: Discovering which protein is altered in one type of cancer Examining cancer cells treated with these chemicals to see their effects Analyzing all of the](https://reader036.vdocuments.us/reader036/viewer/2022062717/56649e495503460f94b3cc62/html5/thumbnails/21.jpg)
Drug A binds to protein target
protein target is altered
Drug B is discovered
Evolution of drug resistance in cancer cells can occur because of changes in the protein target of the drug
This change causes resistance to Drug A.
Drug B can treat cancers resistant to
Drug A.