Transcript Biology of Cancer

Robert A. Weinberg
The Biology of Cancer
First Edition
Chapter 16:
The Rational Treatment of Cancer
Copyright © Garland Science 2007
Figure 16.1a The Biology of Cancer (© Garland Science 2007)
Figure 16.1b The Biology of Cancer (© Garland Science 2007)
Figure 16.2 The Biology of Cancer (© Garland Science 2007)
Figure 16.3 The Biology of Cancer (© Garland Science 2007)
Figure 16.4a The Biology of Cancer (© Garland Science 2007)
Figure 16.4b The Biology of Cancer (© Garland Science 2007)
Figure 16.5a The Biology of Cancer (© Garland Science 2007)
Figure 16.5b The Biology of Cancer (© Garland Science 2007)
Figure 16.5c The Biology of Cancer (© Garland Science 2007)
Figure 16.5d The Biology of Cancer (© Garland Science 2007)
Figure 16.6a The Biology of Cancer (© Garland Science 2007)
Figure 16.6b The Biology of Cancer (© Garland Science 2007)
Figure 16.6c The Biology of Cancer (© Garland Science 2007)
Figure 16.7 The Biology of Cancer (© Garland Science 2007)
Figure 16.8 The Biology of Cancer (© Garland Science 2007)
erbB2/neu amplificated in about 25% of all breast and
ovarian cancers- ”herceptin” targeting ERBB2/HER2
Figure 4.6b The Biology of Cancer (© Garland Science 2007)
Figure 16.9 The Biology of Cancer (© Garland Science 2007)
Table 16.1 The Biology of Cancer (© Garland Science 2007)
Chromosomal Translocation”Philadelphia Chromosome” containing
BCR-ABL fused oncogene
reciprocal exchange
From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings.
Chronic Myelogeous Leukemia (CLM)
Tyrosine kinase activity
Figure 4.15a The Biology of Cancer (© Garland Science 2007)
Figure 16.10a The Biology of Cancer (© Garland Science 2007)
Figure 16.10b The Biology of Cancer (© Garland Science 2007)
It's a cell's most elegant
defender, a gene called p53. It
stops tumors before they
grow. But if damaged, it is
involved in 60 percent of
cancers.
Newsweek, December 23, 1996
p53
The guardian of genome!!!
A tumor suppressor gene
that prevents cells with
damaged DNA from
proliferating
From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings.
p53
From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings.
p53 Tumor Suppressor Protein
Triggers Cell Suicide
p53 protein
Normal cell
Excessive DNA damage Cell suicide
(Apoptosis)
From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings.
DNA damaging
chemicals and
radiation
Tobacco---Lung cells
UVB --- Skin cells
Induce DNA
repair enzymes
Allow cells time
to repair the
damaged DNA
Li-Fraumeni Syndrome
(hereditary p53 mutation)
High risk of getting
mutation of the second
copy of the gene
p53 upregulated modulator
of apoptosis
Mechanism of ubiquitin-mediated proteasomal degradation
From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings.
Loss of Function of p53 may also be caused by viral oncoprotein E6
From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings.
Figure 9.7b The Biology of Cancer (© Garland Science 2007)
Associate w/ p53 binding pocket of Mdm2  p53 stabilization
Figure 16.11a The Biology of Cancer (© Garland Science 2007)
Green Tea:
One of the most promising dietary sources of
chemopreventive phytochemicals
Epidemiological studies revealed an inverse association
between green tea consumption and cancer risk.
EGCG is the major green tea polyphenol with potent
antioxidant and chemopreventive activities.
Studies in animal models have demonstrated the
inhibitory effect of EGCG on carcinogen-induced
tumorigenesis in multiple organs including liver, lungs,
mammary gland, esophagus, and skin.
BcL-XL (Ki 490 nM); Bcl-2 (Ki, 335 nM)
Figure 16.11b The Biology of Cancer (© Garland Science 2007)
APC (Adenomatous polyposis coli)
66% of all colon cancers have APC mutations
Familial adenomatous polyposis
Familial adenocarcinoma
100% risk of developing colon cancer
-Catenin - A molecule linked to various cancers
Also loss of function is associated with nonfamilial colon ca
Nuclear accumulation of -catenin and -catenin -TCF mediated transcription
of several growth regulatory genes were found to be involved in many human
cancers.
Aberrant Growth
Factor Stimuli
Wnt Ligands
Mutation
(APC, Axin, -Catenin)
-Catenin 
 cMyc, Cyclin D1
 Fra1, c-Jun
 Cell Proliferation
From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings.
Inhibition of association beta-catenin-Tcf complex with CBP
Figure 16.11c The Biology of Cancer (© Garland Science 2007)
Binding to proapoptotic Bak
Figure 16.11d The Biology of Cancer (© Garland Science 2007)
Figure 16.12 The Biology of Cancer (© Garland Science 2007)
Figure 16.13a The Biology of Cancer (© Garland Science 2007)
Figure 16.26a The Biology of Cancer (© Garland Science 2007)
Figure 16.26b The Biology of Cancer (© Garland Science 2007)
EGF receptor antagonist
Figure 16.31a The Biology of Cancer (© Garland Science 2007)
Figure 16.43a The Biology of Cancer (© Garland Science 2007)
From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings.