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

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.

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.

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 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 ~10 14 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 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. - information on the particular clinical trial we’re working on. Sometimes MCD Biology dept. has a course on cancer.

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