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Evolution of Cancer
Rebellion within the cell clone collective.
Cancer Overview
• Cancer is disease of uncontrolled cell growth.
• Normally cell growth is tightly controlled
– Growth during development, during pregnancy
– Replacement of worn out cells
• Sometimes cells, generally as a result of mutations,
grow inappropriately -> cancer.
• Cancers can be localized tumors or more
dangerously can metastasize thoughout body.
• Cancer cells have characteristics that can be
exploited in treatment
– Characteristics inherited from normal cell types
– Characteristics that develop during cancerous
transformation
The cell: independent organism
or part of a larger community
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Life as a single cell
• For 1 billion years all life was made of singlecelled organisms.
• Cells react to their environment.
• Other cells are part of their environment.
• Eventually evolved mechanisms to cooperate
rather than compete with their siblings.
• Intensively cooperative colonies of cells became
multicellular organisms.
A Hollow Ball
Volvox - an algae that forms hollow balls. Baby volvox
are forming inside. The hollow ball is more rare than
filaments, but human embryos go through this stage.
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In some organism such as this worm, line of descent of
each cell can be traced back to egg, and the pattern of
differentiation is fixed.
Another Hollow Ball
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The earliest stages of human development from an egg.
Human development is more flexible, depends more on
feedback between cells than worms do. Any cell in inner
cell mass can become a human. Split inner cell masses
lead to identical twins.
Cells that Divide in Adults
• Only a small subset of the cells in an adult
continue to divide.
– Bone marrow (blood) cells.
– Skin, gut, lung and liver cells that isolate us physically
or chemically from outside.
– Cells regenerating damaged areas
– *Tiny* populations of stem cells in heart, brain, other
organs.
– Cells involved with reproduction
• testes, prostrate in men
• Breast, ovaries, uterine lining in women
General pattern of adult stem cells
• Most tissues harbor small population of
stem cells which are capable of dividing.
• One daughter cell stays a stem cell, other
cell differentiates, often dividing a few
more times in process of differentiating.
• It is rare for cancer to occur in a fully
differentiated cell.
Epidermous Cell Layers
The stem cells are in the lowest layer.
Overall a woman has about a 2% chance of developing
breast cancer sometime in her life.
Anatomy of Breast and Ducts
• 95% of breast cancers develop from cells lining
the breast milk ducts.
Evolution of Cancer
• Human body has ~1014 cells from a single egg cell.
• Typical adult cell has gone through ~50 divisions.
• Each division is accompanied by 1-10 errors typically - so
total around 50-500 mutations per cell. But 90% of
mutations will do nothing.
• Additional mutations can occur from UV, radiation, virus,
etc.
• Mutations that favor growth of an individual cell over
survival of the organism lead to cancer.
– Activation of pro-growth “oncogenes”
– Suppression of anti-growth “tumor suppressor genes”
• Occassionally can get cancer without mutation.
– best example is teratoma.
Stages of Cancer
• Minor proliferation of cells in one area “cancer in situ”
• Growth of cells and recruitement of blood
vessels etc. to support growth - “tumor”
• Invasion and destruction of neighboring
tissue - “malignant tumor”
• Spread of cells to new organs - “metastasis”
Treating cancer
• “Watchful waiting” - appropriate for many cancer
in situs and prostrate cancer.
– Many never become serious.
• Surgery - can cure isolated tumors.
• Chemotherapy - required when cancer
metastasizes or is inoperable (brain)
• Radiation - can be used before or after metastasis.
• Vaccines - experimental therapy to get immune
system to fight cancer.
• Standard treatment - surgery followed by chemo.
Characteristics of Cancer Cells
• They divide - generally relatively fast.
• Often
– Have chromosomes are fused/split, with some
deleted and some duplicated.
– Have poor DNA repair mechanisms/high
mutation rates.
– More fragile than normal cells.
– Retain characteristics of normal cells they
descended from
• Many breast cancers require estrogen and/or
progesterone to proliferate
Chemotherapy targets
• Cell division:
– Pro - valid for all cancers.
– Con - bad for bone marrow, gut, hair, etc.
• Recruitment of blood vessels:
– Pro - prevents tumors from getting large. May make
other chemotherapy more effective.
– Con - small tumors can still cause harm. Long term
effects may reduce overall circulation.
• DNA repair:
– Pro - works on many cancers
– Con - not all cancers have repair defects. Stresses other
cells.
• Hormones:
– Pro - relatively non-toxic. (Don’t *need* estrogen).
– Con - doesn’t work on all cancers.
See also
• Wikipedia articles on cancer and breast
cancer are quite good.
• http://tr.nci.nih.gov/iSpy - information on
the particular clinical trial we’re working
on.
• Sometimes MCD Biology dept. has a course
on cancer.
The End