A Sermo Oncologist reported on the Oral (PO) Abstracts session on Leukemia, Myelodysplasia, and Transplantation at ASCO 2015.
I attended an education session entitled Evolution, Medicine, and Cancer. It was a digestible explanation of some of the science behind cancer pathogenesis along with an evolutionary perspective, though it did not reveal any “bombshells” so to speak.
The first speaker was Len Nunney, on “Why do people get cancer?” Longevity is the major risk factor, but size matters, too. For every 10-15 cm increase in height, there is 10-15% increase cancer risk. Size is not everything, and larger animals have evolved cancer suppression mechanisms. Larger rodents have greater telomerase expression, and the naked mole rat (lives 20-30 yrs) has early contact inhibition of growth mediated by INK4. Why does cancer persist? Because natural selection is imperfect. Early-onset (pre-reproduction) cancer happens because deleterious mutations accumulate to a point of equilibrium. Late-onset (post-reproduction) cancer occurs because natural selection is ineffective post-reproduction.
Carlo Maley discussed clonal eolution in metastasis. Tumors evolve by natural selection. Tumors are a mosaic of clones, with hundreds of thousands of mutations, or a “snowflake on steroids”–i.e., unrelenting diversity. Tumors explore a wide range of mutations. In fact, drug resistance probably evolves PRE-treatment. Tumors with more clones have better survival. How do we go after tumors? Scientists are getting inspiration from the extinction literature. To cause extinction, pressures must last longer than several generations, or cell divisions. Single selective pressures are inadequate. Habitats are destroyed. Wide dispersal and motility help tumors evade extinction (i.e. treatment) events. Metastatic cancer is hard to cure because of higher tumor burden, increased mutation accumulation, and the phenomenon of places to hide (refugia) and adaptability to new environments.
Finally, Matthew Breen discussed insights from dogs and sea lions. Comparative sequencing is helping to identify genes potentially involved in genitourinary (esp. bladder) cancer. Purebred dogs are particularly helpful because there is A LOT of genetic homogeneity. Factoid: dogs in the US have 11 times the cancer incidence of humans.
These talks were enjoyable overviews for the non-hardcore scientist. One would need to go to the primary literature for detailed insights into potential molecular targets or responsible drivers of tumorigenesis.
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