The Nature of Cancer

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The Nature of Cancer
All cells have the capacity to
become cancerous
Misusing Normal Tools
Using Abnormal/Broken
Tools
Super Tools
Broken Tools
Cancers are categorized
Categorization of Cancers
Categorization of Cancers
Sarcoma
Carcinoma
Other Cancers
L
M
M
L
L
L
L
Carcinoma
Sarcoma
Cancers develop gradually
normal
metaplasia
Hyperplasia
Metaplasia
normal
Pre-Cancer
malignant
normal
normal
Anaplasia
Epithelial  Mesenchymal Transition (EMT)
normal
Metastasis
Cancers are monoclonal
(or are they????)
?
Supporting Evidence
for Monoclonal Tumors
Barr Bodies
• Chromosome tightly
packaged with proteins
(heterochromatin)
• No gene transcription
from Barr Body
• X chromosomes are
homologous, meaning
that they carry the same
genes, but could carry
different ‘versions’ of
them (alleles)
• X chromosomes carry
~1800 genes
• One of the genes on the X
chromosome encodes
glucose-6-phosphate
dehydrogenase (G6PD)
• There are 2 different alleles
(polymorphisms) in the
human genome, one more
heat resistant than the other.
• 30% of African American
women are heterozygous for
the G6PD gene (they have 2
different alleles in their
genomes)
?
Cancer cells make energy
differently than normal cells
Aerobic Glycolysis = the Warburg Effect
Glycolysis serves other functions
Cancers don’t affect everyone
equally
Genes altered in cancer typically:
• Have a positive role in cell division
• Have a negative role in cell division
• Have a role in the maintenance of DNA integrity
The Behavior of Isolated
(cultured) Cancer Cells
Cancer cells are often described as “transformed.”
Transformed cells behave differently when
cultured than ‘non-transformed’ (normal?) cells.
Technically, cells are considered “transformed” if they exhibit any
one of the following characteristics, and would be considered “more
transformed” with increasing numbers of the following phenotypes:
Transformed versus normal cells:
….in monolayer
normal
normal
transformed
transformed
Transformed versus normal cells:
….in monolayer
Cells exhibit loss of contact dependence; grow independent of cell-to-cell contact
Transformed versus normal cells:
….in suspension
Cells exhibit loss of anchorage dependence;
grow independent of adhesion to a matrix.
Transformed versus normal cells:
….in vivo
Cancers result from alternations
in DNA
Sometimes “genes”, and other times not…but let’s focus on the genes
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