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Transcript of Cancer: Are we closer to a cure? Jesse Boehm, Ph.D. Broad Institute of Harvard and MIT Cambridge,...
![Page 1: Cancer: Are we closer to a cure? Jesse Boehm, Ph.D. Broad Institute of Harvard and MIT Cambridge, MA.](https://reader035.fdocuments.us/reader035/viewer/2022070413/5697bfd51a28abf838cad386/html5/thumbnails/1.jpg)
Cancer:Are we closer to a cure?
Jesse Boehm, Ph.D.
Broad Institute of Harvard and MITCambridge, MA
![Page 2: Cancer: Are we closer to a cure? Jesse Boehm, Ph.D. Broad Institute of Harvard and MIT Cambridge, MA.](https://reader035.fdocuments.us/reader035/viewer/2022070413/5697bfd51a28abf838cad386/html5/thumbnails/2.jpg)
Cancer is a huge public health problem
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Overall mortality rates have not changed for cancer…
586.8
193.9245.8
194.4
0
100
200
300
400
500
600
700
Heart Disease Cancer
Deaths per 100,000 people
1950
2001
* Age-adjusted to 2000 US standard population.Sources: 1950 Mortality Data - CDC/NCHS, NVSS, Mortality Revised.2001 Mortality Data–NVSR-Death Final Data 2001–Volume 52, No. 3.
http://www.cdc.gov/nchs/data/nvsr/nvsr52/nvsr52_03.pdf
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Before Iressa treatment After 3 months of Iressa treatment
But we have made HUGE advances in some cancers!!!!
Image providedby B. Johnson
![Page 5: Cancer: Are we closer to a cure? Jesse Boehm, Ph.D. Broad Institute of Harvard and MIT Cambridge, MA.](https://reader035.fdocuments.us/reader035/viewer/2022070413/5697bfd51a28abf838cad386/html5/thumbnails/5.jpg)
We have made HUGE advances in prevention!!!!
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The Fundamentals of Cancer
What is cancer?
Molecular causes of cancer
How faulty genes are involved
How a cancer cell becomes dangerous
![Page 7: Cancer: Are we closer to a cure? Jesse Boehm, Ph.D. Broad Institute of Harvard and MIT Cambridge, MA.](https://reader035.fdocuments.us/reader035/viewer/2022070413/5697bfd51a28abf838cad386/html5/thumbnails/7.jpg)
What is Cancer?
•An uncontrolled growth of cells
•A genetic disease
•A family of similar diseases
newscenter.cancer.gov
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An Uncontrolled Growth of Cells
•Healthy cells turn into the enemy•divide too quickly or abnormally•become abnormal shapes and sizes•grow in all directions
•Cells stop listening to the body, which is telling them to stop!
.. ... .. ... .. .... . .. ... .. .. .. . .. ..... ..
structuralsupport
dividing cells
non-dividing cells
normalskin
skin cancer
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A Genetic Disease
Normal Cells Cancer Cells
•Mutations in DNA can make normal cells become cancerous
•These can be inherited or spontaneous
.. ... .. ... .. .... . .. .
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A Family of Similar Diseases
•Carcinomas: from cells which protect the body from air and internal fluids
•Sarcomas: from cells in supportive tissue
•Leukemias and Lymphomas: from cells in the blood andimmune system
newscenter.cancer.gov
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The Fundamentals of Cancer
What is cancer?
Molecular causes of cancer
How faulty genes are involved
How a cancer cell becomes dangerous
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Common causes of cancer
•Chemicals (e.g. tobacco, asbestos)•Viruses (e.g. HPV) •Radiation from the sun
What do all of these have in common?
They all lead to MUTATIONS in the DNA of your cells
They are called MUTAGENS
Can also be predisposed to getting cancer by inheriting mutations from parents
newscenter.cancer.gov
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Smoking and AlcoholCigarette smoking causes 87 percent of lung cancer deaths and
is responsible for most cancers of the larynx, oral cavity and pharynx, esophagus, and bladder
Tobacco smoke contains thousands of chemical agents, including over 60 substances that are known to cause cancer.
Alcohol use has been implicated in the development of a number of cancers • Risk increases >1 drink for women or 2 drinks for men/day
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Causes of Cancer
Cancer Cells
What are mutations and how do they cause normal cells to become
cancer cells?
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How Could a Mutant Protein Make Cells Divide Out of Control?
mutant protein cancer cells
?
mutant DNA
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What Happens Normally?
DNA Bases
Normal DNA
A T
C G
CG
A T
CG
A T
C G
A
A
T
T
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Normal DNA
What Happens Normally?
A T
C G
CG
A T
CG
A T
C G
A
C
G
A
G
A
C
mRNA
DNA is transcribed (copied) to RNA
A
A
T
T
A
A
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What Happens Normally?
Normal Protein
mRNA
Translation: Proteins are made from mRNA
aminoacids
Normal DNA
A T
C G
CG
A T
CG
A T
C G
A
C
G
A
G
A
C
A
A
T
T
A
A
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A T
C G
CG
A T
CG
Changed DNA
A T
C G
DELETION
A Mutation Occurs
A T
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Changed DNA
A Mutant Protein is Made
A T
C G
CG
A T
CG
A T
C G
A
C
G
A
G
A
C
Changed mRNA
DELETION
Normal Protein
Abnormal/ Mutant Protein
A T
A
A
AA T
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A Mutant Protein is Made
Normal Protein
Changed DNA
A
T
C G
CG
A T
CG
C G
A
T
Abnormal/ Mutant Protein
A T
A T
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How Could a Mutant Protein Make Cells Divide Out of Control?
mutant protein cancer cells
?
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The Cell Cycle Controls Cell Division
Cell Cycle
Cells divide (mitosis)
DNA Synthesis
Growth
Growth
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The Cell Makes Sure That There are no Problems
Cell Cycle
Did division go correctly?
Is my DNA copied
correctly?
Am I big enough?
Am I ready to divide?
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The Cell Cycle Has Checkpoints
Cell Cycle
Did division go correctly?
Is my DNA copied
correctly?
Am I big enough?
Am I ready to divide?
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The Normal Protein Functions at a Cell Cycle Checkpoint
Cell Cycle
Normal Protein
Is my DNA copied correctly?
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The Mutant Protein Allows The Cell to Divide Out of Control
Cell Cycle
I can’t stop and check if the DNA has been copied
correctly!!!
Normal Protein
Abnormal/ Mutant Protein
go!
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The Fundamentals of Cancer
What is cancer?
Molecular causes of cancer
How faulty genes are involved
How a cancer cell becomes dangerous
![Page 29: Cancer: Are we closer to a cure? Jesse Boehm, Ph.D. Broad Institute of Harvard and MIT Cambridge, MA.](https://reader035.fdocuments.us/reader035/viewer/2022070413/5697bfd51a28abf838cad386/html5/thumbnails/29.jpg)
How Faulty Genes are Involved
Not every gene leads to cancer when mutated
Mutations in two specific categories of genes can lead to cancer
• Tumor-Suppressor Genes
• Oncogenes
![Page 30: Cancer: Are we closer to a cure? Jesse Boehm, Ph.D. Broad Institute of Harvard and MIT Cambridge, MA.](https://reader035.fdocuments.us/reader035/viewer/2022070413/5697bfd51a28abf838cad386/html5/thumbnails/30.jpg)
How Faulty Genes are Involved
Not every gene leads to cancer when mutated
Mutations in two specific categories of genes can lead to cancer
• Tumor-Suppressor Genes
• Oncogenes
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Inactivated Tumor Suppressor Genes Lead to Cancer
•Tumor Suppressor (TS) genes normally inhibit cell growth
•Mutations in TS genes may inactivate them, so that they cannot stop cell-growth
•TS genes include p53 and BRCA1/2
cell TS gene
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How Faulty Genes are Involved
Not every gene leads to cancer when mutated
Mutations in two specific categories of genes can lead to cancer
• Tumor-Suppressor Genes
• Oncogenes
![Page 33: Cancer: Are we closer to a cure? Jesse Boehm, Ph.D. Broad Institute of Harvard and MIT Cambridge, MA.](https://reader035.fdocuments.us/reader035/viewer/2022070413/5697bfd51a28abf838cad386/html5/thumbnails/33.jpg)
Activated Oncogenes Lead to Cancer
•Oncogenes normally promote cell growth carefully
•Mutations in oncogenes may over-activate them, so that they always promote cell-growth
•One well-known oncogene is called RAS
cell oncogene
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Mutations in Specific Genes Turn a Normal Cell into a Cancer Cell
Mutate tumor suppressor genes, turning these genes OFF
Mutate oncogenes, turning these genes ON
normal cell cancer cell
mutations
1 2 3 4 5 6…..
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The Fundamentals of Cancer
What is cancer?
Molecular causes of cancer
How faulty genes are involved
How a cancer cell becomes dangerous
![Page 36: Cancer: Are we closer to a cure? Jesse Boehm, Ph.D. Broad Institute of Harvard and MIT Cambridge, MA.](https://reader035.fdocuments.us/reader035/viewer/2022070413/5697bfd51a28abf838cad386/html5/thumbnails/36.jpg)
Benign vs. Malignant
Benign: A non-malignant tumor lacking the ability to invade surrounding normal tissue
Malignant: A tumor that tends to grow, has the capacity to invade nearby tissue and spreads through the blood stream
adapted from “Concise Dictionary of Biomedicine and Molecular Biology,” Pei-Show Juo, 1996
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How cancer cells become dangerous
•A cancer cell on its own will not cause you harm
•To become the disease “Cancer” the cell must:
•1) Form a tumor (at least)
•2) Recruit a blood supply = angiogenesis(solid tumors only)
•3) Spread to other parts of the body = metastasis (advanced stages)
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Metastasis
Cells then invade new tissues, and
begin to grow
Cells travel through the blood stream to
distant sites
Cancer cells enter blood vessels
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Cancer treatment
Tumor
Lung
Heart
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Surgery
Radiation
Drugs (chemotherapy)
There are different types of treatments
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Cancer can be local or metastatic
local (one primary
tumor)
metastatic (secondary
tumors)
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Cancer therapy: local and systemic
LOCAL: surgery and
radiation
SYSTEMIC: chemotherapy,
etc.
Rx
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The problem of Selectivity of chemotherapy and radiation
Why need targeted therapy?
cancer cellsnormal cells
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The problem of Selectivity of chemotherapy and radiation
Why need targeted therapy?
cancer cellsnormal cells
![Page 45: Cancer: Are we closer to a cure? Jesse Boehm, Ph.D. Broad Institute of Harvard and MIT Cambridge, MA.](https://reader035.fdocuments.us/reader035/viewer/2022070413/5697bfd51a28abf838cad386/html5/thumbnails/45.jpg)
The problem of Selectivity of chemotherapy and radiation
Why need targeted therapy?
cancer cellsnormal cells
![Page 46: Cancer: Are we closer to a cure? Jesse Boehm, Ph.D. Broad Institute of Harvard and MIT Cambridge, MA.](https://reader035.fdocuments.us/reader035/viewer/2022070413/5697bfd51a28abf838cad386/html5/thumbnails/46.jpg)
Killing a fly with a cannon ball?
![Page 47: Cancer: Are we closer to a cure? Jesse Boehm, Ph.D. Broad Institute of Harvard and MIT Cambridge, MA.](https://reader035.fdocuments.us/reader035/viewer/2022070413/5697bfd51a28abf838cad386/html5/thumbnails/47.jpg)
We can kill the fly but…
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Problem with selectivity leads to side effects
SIDE EFFECTS!
• hair follicles: hair loss • bone marrow: immune defense,
anemia, clotting problems• gut lining: diarrhea• skin: flaky/scaly skin
cancer cellsnormal cells
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How can we improve cancer therapy?
Pick a better TARGET!
Normal cell Cancer cell
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Points to rememberCancer is a family of similar diseases, not just one!
Different cancers have different causes, treatments and outcomes
Cancer is caused by MUTATIONS• Prevent your exposure to mutagens!
A tumor causes a patient harm by becoming malignant and metastasizing
By learning more about cancer we are developing new,
“smarter” cancer drugs More effective Fewer side effects
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Thank you!