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More Human Than Human The Evolution of Cancer By Chris Engdahl

More Human Than Human The Evolution of Cancer By Chris Engdahl. The Facts (Light). Over 200 known types 13% of all deaths (7.6 million in 2007) ~ 1 in 6 will get it Found in all plants Found in all animals. Are we looking at this from the wrong perspective?. Traditional Perspectives

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More Human Than Human The Evolution of Cancer By Chris Engdahl

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  1. More Human Than HumanThe Evolution of CancerBy Chris Engdahl

  2. The Facts (Light) • Over 200 known types • 13% of all deaths (7.6 million in 2007) • ~ 1 in 6 will get it • Found in all plants • Found in all animals

  3. Are we looking at this from the wrong perspective? Traditional Perspectives Why is cancer so prevalent? Why can’t we always treat it? Why can’t we seem to win the war? Evolutionary Perspectives How does evolutionary theory pertain to cancer? How can we use evolution to plan and model our treatments?

  4. Proximate Causation Lifestyle Pathogens Carcinogens Genetic Abnormalities

  5. Proximate Causation • Self Sufficient Growth • Evades Apoptosis • Antigrowth Signal Failure • Angiogenesis • Limitless Reproduction • Metastasis Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000 Jan 7;100(1):57-70.

  6. Proximate Causation This is not necessarily a linear process Most of us have already had precancerous growths and survived (why?) Hanahan, et al (2000)

  7. Ultimate Causation • Occurs in all animals • Children/youth have extremely low rates • Rarely occurs during reproductive ages • Cancer is a disease of aging Could this be an example of…

  8. Antagonistic Pleiotropy “Can I get an AMEN?”

  9. Antagonistic Pleiotropy “Natural selection will frequently maximize vigor in youth at the expense of vigor later on and thereby produce a declining vigor (senescence) during adult life.” George C. Williams Williams, G.C. 1957. Pleiotropy, natural selection, and the evolution of senescence. Evolution 11:398–411.

  10. Antagonistic Pleiotropy Natural selection favors strong anticancer defenses through our reproductive ages This protects our bodies and genomes just enough for us to maximize our reproductive potential As our “vigor” ends, we have no need to maintain our systems (Disposable Soma Hypothesis) A universal trait (So those without it quickly were selected against)

  11. And to a lesser degree… Gene-environment mismatch (Diet) Cellular level reproductive advantage Pathogen virulence (XMRV vs HPV) Demographic effects (Occupations, cultural practices, geography)

  12. Cancer = Evolution • Heritable changes in the genome • Cancer cells have an adaptive advantage • Unequal reproduction (Cancers outcompete normal cells) • Natural selection • Evolution of population (good for them, bad for us)

  13. Treating Cancer = Evolution • Chemotherapy • Targeted therapy • Surgery • Gene therapy • Radiation Therapy …are examples of selective pressures we apply to cancer

  14. Complications = Evolution • Metastasis - Neoplasm outcompetes and invades our normal cells • Drug resistance - Tumors stop responding to treatments (i.e. ABCB1 proteins pump chemotherapy out of cells) …are examples of selective pressures cancer applies to us!

  15. Is There Hope? If cancer is an evolutionary process, why not use evolutionary theory to fight it?

  16. Evolution Based Treatments Vaccinations (+) Highly effective in some models (i.e. HPV/Gardasil) if inoculated preexposure (-) Useless against novel pathogens or the non-pathogenically derived cancers Multi-drug Chemotherapy (+) Prevents emergence of resistant strains (-) Expensive, lack of comparable drugs in arsenal

  17. Evolution Based Treatments • Oncolytic viruses (Viral antagonists) (+) Highly selective, outcompetes even cancer cells (-) May elicit immune response. Pathogenicity potential • Anaerobic bacteria (Clostridium novyi) (+) Targets and kills anaerobic nuclei of tumors (-) Ineffective against aerobic cancers (But useful in “boosting” chemotherapy) • Environmental manipulation (e.g. Focused hyperthermia, antiangiogenic therapies) (+) Tumors are more susceptible to change than normal cells (-) Doesn’t often kill cells (may only weakens them)

  18. The Take Home Cancer is an evolutionary process Cancer is a disease of senescence Postreproductively, antagonistic pleiotropy makes our soma “expendable” Treatments should reflect this understanding

  19. Citations • Fan H. (2007) A new human retrovirus associated with prostate cancer. Proc Natl Acad Sci U S A; 104:1449–50. • Hanahan D, Weinberg RA (2000). The hallmarks of cancer. Cell. Jan 7;100(1):57-70. • Jain RK, Forbes NS (2001). "Can engineered bacteria help control cancer?". Proc. Natl. Acad. Sci. U.S.A. 98 (26): 14748–50. • Kanerva A, Lavilla-Alonso S, Raki M, et al. (2008). "Systemic therapy for cervical cancer with potentially regulatable oncolytic adenoviruses". PLoS ONE 3 (8): e2917. • Mengesha et al. (2009). "Clostridia in Anti-tumor Therapy". Clostridia: Molecular Biology in the Post-genomic Era. Caister Academic Press • Pepper JW, Findlay CS, Kassen R, Spencer SL, Maley CC (2009). "Cancer research meets evolutionary biology". Evol. Appl. 2: 62–70. • Rein DT, Breidenbach M, Curiel DT (February 2006). "Current developments in adenovirus-based cancer gene therapy". Future Oncol 2 (1): 137–43 • Ring A, Dowsett M (December 2004). "Mechanisms of tamoxifen resistance". Endocr. Relat. Cancer 11 (4): 643–58. • Rodier F, Campisi J, Bhaumik D (2007). "Two faces of p53: aging and tumor suppression". Nucleic Acids Res 35: 7475. • Urisman, R.J. Molinaro, N. Fischer, S.J. Plummer, G. Casey and E.A. Klein et al., (2006) Identification of a novel Gammaretrovirus in prostate tumors of patients homozygous for R462Q RNASEL variant. PLoS Pathog 2 (3) • Williams, G.C. (1957). Pleiotropy, natural selection, and the evolution of senescence. Evolution 11:398–411.

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