Download Treating cancer:

•Homework #3 is due 11/15
•Bonus #2 is posted
•No class on 11/20
Mitosis is tightly regulated: checkpoints
A cell becomes cancerous
when there are incorrect
positive AND negative
signals.
GO!
STOP!
cancer
similar to Fig 15.36
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
Treating cancer:
• Avoid it
– Avoid mutagens
– DNA repair gets less efficient as we age
Environment plays a
large role in the chance
of contracting cancer.
Our immune system protects us from cancer
T-cells recognize and eliminate abnormal
cells; such as cells with many mutations
P53 is activated by DNA damage
p53 can induce apoptosis via two pathways:
Nuclear and/or Mitochondrial
Treating cancer:
• Avoid it
– Avoid mutagens
– DNA repair gets less efficient as we age
• Surgery
– Must remove all cancer cells
– Non-invasive
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
-> cellular self-destruction
– Mutagenic, side effects
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
Chemotherapy
X
X
a rapidly dividing cell
Normal Multi-Drug Resistance protein
toxin/hormone/etc
MDR
MDR
toxin/hormone/etc
toxin/hormone/etc
MDR
toxin/hormone/etc
MDR
toxin
toxin
toxin
MDR
MDR
MDR
MDR
MDR
MDR
MDR
MDR
MDR
MDR
toxin
toxin
toxin
toxin
toxin
toxin
I’m a cancer cell with
over-expressing MDR.
I laugh at your toxins.
MDR
toxin
toxin
MDR
toxin
Some cancers over-express MDR
Mutations continue after cancer develops
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
The Epigenetic Progenitor Origin of Human Cancer (2007) A P Feinberg, R Ohlsson, S Henikoff Nature Reviews Genetics 7: 21-31
Evolution: changes in DNA as information transmitted
O
O
O
O
O
O
O
O
O
O
O
Cancer cell with
mutation causing
MDR over-production
Evolution: changes in DNA as information transmitted
O
O
O
O
O
O
O
O
O
O
O
Apply
chemotherapy
X
O
O
O
X
X
O
X
X
X
O
O
X
X
O
X
X
O
O
O
O
Kills most cells.
Except if some have mutation
that allow them to be resistant.
Cancer cell with
mutation causing
MDR over-production
Evolution: changes in DNA as information transmitted
O
O
O
O
O
O
O
O
O
O
O
Apply
chemotherapy
O
X
O
O
O
X
X
O
X
X
X
O
O
X
X
O
X
O
O
O
O
Kills most cells.
Except if some have mutation
that allow them to be resistant.
X
Cancer cell with
mutation causing
MDR over-production
Continues to
replicate
Evolution: changes in DNA as information transmitted
O
O
O
O
O
O
O
O
O
O
O
Cancer cell with
mutation causing
MDR over-production
Apply
chemotherapy
O
X
O
O
X
O
O
O
O
Kills most cells.
Except if some have mutation
that allow them to be resistant.
X
O
O
X
X
O
X
X
X
O
O
X
X
O
Continues to
replicate
O
O
O
O
O
O
O
O
O
O
Tumor with cells expressing MDR
toxin
toxin
toxin
MDR
MDR
MDR
MDR
MDR
MDR
MDR
MDR
MDR
MDR
toxin
toxin
toxin
toxin
toxin
toxin
I’m a cancer cell with
over-expressing MDR.
I laugh at your toxins.
MDR
toxin
toxin
MDR
toxin
Some cancers over-express MDR
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
Tumors must have
sufficient blood flow to
continue cell division
induce blood
vessel growth
(angiogenesis)
Tumors Evolve: Only tumor cells near blood
vessels or that can attract blood vessels
survive.
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.
Detecting
Cancer or
Types of
Cancer
Fig 13.18-19
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.
Tracking changes in gene expression using a
Microarray
Making cDNA
from RNA
Tracking changes in gene expression using a
Microarray
Tracking
changes in gene
expression using
a Microarray
Use of microarray to estimate genes likely
present in malignant cancers
Use of microarray to estimate genes likely
different genes
present in malignant cancers
Patients
cancer
free for
5+ years
Patients
cancer
spread in
5 years
similar to Fig 13.18-19
Young (>55) Breast cancer patients
More accurate
profiling of
tumors results in
more accurate
choices of
treatments.
Patients with
benign tumors can
avoid
chemotherapy
(adjuvant).
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 Lam
BMC Genomics, 8:297
Table 1: Subject Demographics
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
CS=current smoker, FS=former smoker, NS=never smoked
Effect of active smoking on the human bronchial epithelium transcriptome (2007) R Chari et el. BMC Genomics, 8:297
Overlapping and unique genes expression
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
Effect of active smoking on the human
bronchial epithelium transcriptome (2007)
R Chari et el. BMC Genomics, 8:297
Fig 1B
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, 8:297
Some changes in gene expression induced by
smoking are reversible
CABYR
ENTPD8
TFF3
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
Effect of active smoking on the human bronchial epithelium transcriptome (2007) R Chari et el. BMC Genomics, 8:297
Fig 4A
Smoking can induce irreversible changes in
gene expression
MUC5AC
GSK3B
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
Effect of active smoking on the human bronchial epithelium transcriptome (2007) R Chari et el. BMC Genomics, 8:297
Fig 4B
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
•Homework #3 is due 11/15
•Bonus #2 is posted
•No class on 11/20