Treating cancer:

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• Homework 3 is due 11/15
• Bonus 2 is posted
• No class on 11/20

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Mitosis is tightly regulated checkpoints
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A cell becomes cancerous when there are incorrect
positive AND negative signals.
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GO!
STOP!
cancer
similar to Fig 15.36
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Causes of mutations

• Replication errors
• Exacerbated by poor DNA repair
• Limited by telomere length
• Other biological agents
• Viruses
• Transposons
• Environmental factors
• Ultraviolet light
• Mutagenic chemicals
• smoking, industrial waste, natural toxins

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Treating cancer

• Avoid it
• Avoid mutagens
• DNA repair gets less efficient as we age

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Environment plays a large role in the chance of
contracting cancer.
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Our immune system protects us from cancer
T-cells recognize and eliminate abnormal cells
such as cells with many mutations
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P53 is activated by DNA damage
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p53 can induce apoptosis via two pathways
Nuclear and/or Mitochondrial
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Treating cancer

• Avoid it
• Avoid mutagens
• DNA repair gets less efficient as we age
• Surgery
• Must remove all cancer cells
• Non-invasive

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Treating cancer

• Avoid it
• Avoid mutagens
• DNA repair gets less efficient as we age
• Surgery
• Must remove all cancer cells
• Non-invasive
• Radiation
• Directed at tumor causes DNA damage
• -gt cellular self-destruction
• Mutagenic, side effects

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Treating cancer

• Avoid it
• Avoid mutagens
• DNA repair gets less efficient as we age
• Surgery
• Must remove all cancer cells
• Non-invasive
• Radiation
• Directed at tumor
• Mutagenic, side effects
• Chemotherapy
• Toxins directed at rapidly dividing cells
• Mutagenic, many side effects

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Chemotherapy
Toxin
X
X
a rapidly dividing cell
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Normal Multi-Drug Resistance protein
toxin/hormone/etc
MDR
toxin/hormone/etc
toxin/hormone/etc
MDR
MDR
MDR
toxin/hormone/etc
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Some cancers over-express MDR
toxin
toxin
toxin
toxin
Toxin
MDR
MDR
MDR
MDR
Im a cancer cell with over-expressing MDR. I
laugh at your toxins.
MDR
toxin
toxin
MDR
toxin
MDR
toxin
MDR
MDR
MDR
MDR
MDR
toxin
toxin
toxin
toxin
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Mutations continue after cancer develops
The Epigenetic Progenitor Origin of Human Cancer
(2007) A P Feinberg, R Ohlsson, S Henikoff
Nature Reviews Genetics 7 21-31
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Evolution changes in DNA as information
transmitted
O
O
O
Cancer cell with mutation causing MDR
over-production
O
O
O
O
O
O
O
O
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Evolution changes in DNA as information
transmitted
O
O
O
Cancer cell with mutation causing MDR
over-production
O
O
O
O
O
O
O
O
Apply chemo-therapy
X
X
X
O
O
O
X
X
X
O
O
O
O
X
X
X
X
O
O
O
O
Kills most cells. Except if some have mutation
that allow them to be resistant.
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Evolution changes in DNA as information
transmitted
O
O
O
Cancer cell with mutation causing MDR
over-production
O
O
O
O
O
O
O
O
Apply chemo-therapy
Continues to replicate
O
X
X
X
O
O
O
X
X
X
O
O
O
O
X
X
X
X
O
O
O
O
Kills most cells. Except if some have mutation
that allow them to be resistant.
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Evolution changes in DNA as information
transmitted
O
O
O
Cancer cell with mutation causing MDR
over-production
O
O
O
O
O
O
O
O
Apply chemo-therapy
Continues to replicate
O
X
X
X
O
O
O
X
X
X
O
O
O
O
O
O
O
O
O
O
O
X
X
X
X
O
O
O
O
Kills most cells. Except if some have mutation
that allow them to be resistant.
O
O
O
O
Tumor with cells expressing MDR
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Some cancers over-express MDR
toxin
toxin
toxin
toxin
Toxin
MDR
MDR
MDR
MDR
Im a cancer cell with over-expressing MDR. I
laugh at your toxins.
MDR
toxin
toxin
MDR
toxin
MDR
toxin
MDR
MDR
MDR
MDR
MDR
toxin
toxin
toxin
toxin
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One of the latest chemotherapy treatments
involves cutting off the blood supply to the
tumor.(anti-angiogenesis)
Cells need the proximity of blood vessels to
survive
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Tumors must have sufficient blood flow to
continue cell division
induce blood vessel growth (angiogenesis)
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Tumors Evolve Only tumor cells near blood
vessels or that can attract blood vessels survive.
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Targeting toxins to cancer cells
A vesicle with mutant genes that cause blood
vessels to die is directed to newly growing blood
vessels by interacting with Integrins. Integrins
are present on newly growing blood vessels, but
not on established blood vessels.
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Detecting Cancer or Types of Cancer
Fig 13.18-19
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A Microarray is a chip with DNA sequences (genes)
bound to the surface at known locations.
It can be used to track or monitor expression of
many genes.
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Tracking changes in gene expression using a
Microarray
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Making cDNA from RNA
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Tracking changes in gene expression using a
Microarray
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Tracking changes in gene expression using a
Microarray
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Use of microarray to estimate genes likely
present in malignant cancers
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Use of microarray to estimate genes likely
present in malignant cancers
different genes
Patients cancer free for 5 years
Patients cancer spread in 5 years
similar to Fig 13.18-19
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Young (gt55) Breast cancer patients
More accurate profiling of tumors results in more
accurate choices of treatments. Patients with
benign tumors can avoid chemotherapy (adjuvant).
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Effect of active smoking on the human bronchial
epithelium transcriptome (2007)R Chari, K M
Lonergan, R T Ng, C MacAulay, W L Lam, and S
LamBMC Genomics, 8297
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Table 1 Subject Demographics
CScurrent smoker, FSformer smoker, NSnever
smoked
Effect of active smoking on the human bronchial
epithelium transcriptome (2007) R Chari et el.
BMC Genomics, 8297
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Overlapping and unique genes expression
Effect of active smoking on the human bronchial
epithelium transcriptome (2007) R Chari et el.
BMC Genomics, 8297
Fig 1B
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Table 3 Reversible gene expression upon smoking
cessation related to mucus secretion (genes in
bold have not been previously associated with
smoking)
Effect of active smoking on the human bronchial
epithelium transcriptome (2007) R Chari et el.
BMC Genomics, 8297
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Some changes in gene expression induced by
smoking are reversible
CABYR
ENTPD8
TFF3
Fig 4A
Effect of active smoking on the human bronchial
epithelium transcriptome (2007) R Chari et el.
BMC Genomics, 8297
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Smoking can induce irreversible changes in gene
expression
MUC5AC
GSK3B
Fig 4B
Effect of active smoking on the human bronchial
epithelium transcriptome (2007) R Chari et el.
BMC Genomics, 8297
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Treating cancer

• Avoid it
• Avoid mutagens
• DNA repair gets less efficient as we age
• Surgery
• Must remove all cancer cells
• Non-invasive
• Radiation
• Directed at tumor
• Mutagenic, side effects
• Chemotherapy
• Toxins directed at rapidly dividing cells
• Mutagenic, many side effects

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• Homework 3 is due 11/15
• Bonus 2 is posted
• No class on 11/20