Cancer clippings

Evolving drug resistance, etc

• Nature news: Why a person doesn't evolve in one lifetime
• EurekAlert: To evade chemotherapy, some cancer cells mimic stem cells

Series on tumour adaptations / barriers to proliferation

1. Introduction to the series
1. Introduction to cancer cell and molecular biology and genetics: cancer as a genetic disease; cancer as a disease of cell-cycle regulation; oncogenes, TSGs, apoptosis and DNA repair mechanisms
2. Introduction to evolution: populations in an environment; the conditions for evolution, proliferation, imperfect replication, competition; the gene-centered view; evolution in the individual as we age; evolution is not teleological
2. Introduction to tumour evolution and the adaptations we see:
1. the microenvironment and the selection pressures it produces (hypoxia central amongst them)
2. why cancer is not "microevolution" but a minuture version of "macroevolution" in terms of population and ecology
3. Knudsen multi-hit
4. chromosomal instability
5. cancer stem cells
6. perhaps an item on chromatin/epigenetics/methylation
3. A post on each of the common adaptations (include cellular and molecular details, drugs that target them, etc):
1. Loss of DNA checkpoints (pre- and post- replication) and repair mechanisms (p53, BRCA, predispositions, link to chromosomal instability and things like Bloom syndrome?)
2. Dysregulation of cell-cycle (oncogenes and TSGs w. her2+rb examples?, CDCs, CDKs, cyclins)
3. Loss of apoptosis (include intro to telomeres here?)
4. Stealing nutrients: dysregulated glycolysis, anaerobic respiration
5. Angiogenesis and vasculogenesis (vegf, link to the DS stuff, anti-angiogenic drugs)
6. Dodging the immune system (include how radiotherapy counters this)
7. Invasion and metastasis (MMPs)
8. Drug resistance (link back to pharmacogenomics)
4. Convergent evolution: discuss how it differs in cancer compared to in the field (more homogenous environment, more homogenous starting point).
5. Side series: important and quirky people in the story:
1. Cell-cycle: Hunt, Nurse, and Hartwell
2. Apoptosis: Folkman

Possible sources:

• Misc: A microenvironmental model of carcinogenesis
• Glycolysis:
• Adaptive landscapes and emergent phenotypes: why do cancers have high glycolysis?