Evolution of Cancer

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Evolution of Cancer
Rebellion within the cell clone collective.
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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 -gt 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

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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
  single-celled 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.

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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.
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Another Hollow Ball
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.
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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

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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.

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Epidermous Cell Layers

• The stem cells are in the lowest layer.

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Overall a woman has about a 2 chance of
developing breast cancer sometime in her life.
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Anatomy of Breast and Ducts

• 95 of breast cancers develop from cells lining
  the breast milk ducts.

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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.

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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

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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.

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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

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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. (Dont need
  estrogen).
• Con - doesnt work on all cancers.

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See also

• Wikipedia articles on cancer and breast cancer
  are quite good.
• http//tr.nci.nih.gov/iSpy - information on the
  particular clinical trial were working on.
• Sometimes MCD Biology dept. has a course on
  cancer.

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The End