Cancer Genetics

From Hawaiʻi Reed Lab
Revision as of 19:51, 23 April 2019 by Floyd (talk | contribs) (The importance of pure research)
(diff) ← Older revision | Latest revision (diff) | Newer revision → (diff)
Jump to navigation Jump to search

I (Floyd Reed) am working on finishing up two manuscripts that touch upon aspects of cancer genetics and recently gave a guest lecture about cancer genetics in an undergraduate biology class. While I am actively thinking about it I want to collect some notes and resources together here.

Notes from a guest lecture on cancer genetics

Most people have direct personal experience with cancer. Either they themselves, a family member, or a close friend has been affected by cancer.

Briefly review mitosis and the cell cycle.

Give an example of the interactions of pRB, E2F, Cyclin D1, and Cdk4.

Introduce Retinoblastoma.

Cdk and cyclin amplification (multiple copies) and hyperactivation (overexpression) to oncogenes.

Introduce p53.

The discovery of cyclins.

Cell cycle control regulatory network and Rube-Goldberg Machines

Self resetting machines.

wee1- rum1- double mutant.

Cancer is a breakdown of cellular cooperation in multicellular organisms.

Cells in multicellular organisms depend extensively on signals from other cells (like growth signals, cell death, etc.).

Example of Notch Delta

Enabling processes in the development of cancer.

Development of a benign tumor.

Transition of a benign tumor into a malignant tumor.

Two general gene categories, oncogenes and tumor suppressors.

What increases the rates of cancer?

Rous sarcoma virus example.

Inherited components versus environmental causes.

Lifetime risk of cancer.

Rates of cancer over the last 100 years.

The lag time between smoking and lung cancer

Cancer incidence and age

Cancer across the tree of life

Peto’s paradox

Several factors have made cancer hard to study in the past. One of these may be that traditional model organisms are, unlike humans, short lived. In many ways cancer is a disease of age and possibly body size. Insights have come from studying a range of non-traditional long-lived species.

Elephants, Naked Mole Rats, Plants

Transmissible cancer

Tasmanian devils, shellfish.

Could free living cancer cells survive and evolve?

Could cancer cells survive in sea water on their own and escape from their host? (Myxosporea?)

Cancer and speciation

platyfish-swordtail hybrid melanoma

Beyond cells, cancer in super-organisms

Broadening our focus: social cancer of super-organisms?

The importance of the immune system in cancer

The importance of pure research

Peyton Rous was interested in natural history and later pathology. He investigated a tumor in a hen brought by a person to the institute where he worked and could not have known that his work would identify oncogenic viruses; it lead him on a path that also identified chemical carcinogens, two distinct stages of carcinogenesis, and ultimately resulted in the Nobel prize (Weiss and Vogt 2011).

Tim Hunt happened to be working on getting sea urchin eggs to divide without being fertilized and noticed an odd pattern of a protein that appeared and disappeared with each cell division. It is sobering to read Hunt (2015) and Robertson (2015) in the context of current academic research culture, also listen to Al-Khalili (2011) for an audio interview. There were a series of chance events that led to the discovery of cyclins that control the cell cycle, difficulty in getting the scientific community to realize the significance, had implications for understanding cancer, and ultimately resulted in the Nobel Prize.

More recent breakthroughs have been in the interface between the immune system and cancer. “Neither of the two Nobel Prize winners, Jim Allison and Tasuku Honjo, directly set out to cure cancer – “that wasn’t it at all,” Allison has said – they were trying to understand how the immune system works” (Davis 2019).

By all means research focused on cancer should be funded from governmental and private sources (donate to the American Cancer Society, https://www.cancer.org/). However, we should also not discount the real breakthroughs that stem from fundamental biological research without immediate applications in mind. If you want to cure cancer fund biology. (The budget for the National Cancer Institute for fiscal year 2019 is $5.74 billion, https://www.cancer.gov/about-nci/budget , by comparison the 2018 fiscal year budget for all "Biological Sciences" by the National Science Foundation is $0.75 billion, https://www.nsf.gov/about/congress/115/highlights/cu18_fy18approps.jsp .)

Classes here at UH Mānoa

BIOL/MCB 472 Biology of Cancer, Howard Shen.

References

  • Aktipis, C. A., Boddy, A. M., Jansen, G., Hibner, U., Hochberg, M. E., Maley, C. C., & Wilkinson, G. S. (2015). Cancer across the tree of life: cooperation and cheating in multicellularity. Philosophical Transactions of the Royal Society B: Biological Sciences, 370(1673), 20140219.
  • Al-Khalili, J. (2011). The Life Scientific: Tim Hunt. BBC Radio 4. BBC. https://www.bbc.co.uk/programmes/b0184rfy
  • Albuquerque, T. A., Drummond do Val, L., Doherty, A., & de Magalhães, J. P. (2018). From humans to hydra: patterns of cancer across the tree of life. Biological Reviews, 93(3), 1715-1734.
  • Callaway, E. (2015). How elephants avoid cancer. Nature, 1038, 18534.
  • Choi, C. Q. (2016). In Shellfish, Cancer Can Be Contagious. Live Science https://www.livescience.com/55156-transmissable-cancer-found-in-shellfish.html
  • Davidich, M. I., & Bornholdt, S. (2008). Boolean network model predicts cell cycle sequence of fission yeast. PloS one, 3(2), e1672.
  • Davis, D. (2020 (article accessed in 2019, date is inaccurate)). Why your immune system is key in the fight against cancer. WIRED Health https://www.wired.co.uk/article/immune-system-cancer
  • Dobata, S., Sasaki, T., Mori, H., Hasegawa, E., Shimada, M., & Tsuji, K. (2011). Persistence of the single lineage of transmissible ‘social cancer’in an asexual ant. Molecular ecology, 20(3), 441-455.
  • Doonan, J. H., & Sablowski, R. (2010). Walls around tumours—why plants do not develop cancer. Nature Reviews Cancer, 10(11), 794.
  • Hanahan, D., Weinberg, R. A. (2000). The Hallmarks of Cancer. Cell 100(1): 57–70.
  • Hanahan, D., Weinberg, R. A. (2011). Hallmarks of Cancer: The Next Generation. Cell 144(5): 646–674.
  • Hunt, T. (2015). Pursuing the impossible: an interview with Tim Hunt. BMC biology, 13(1), 64.
  • Mannino, A. C., Ruzzon, T., Lercari, S., & Uccelli, S. (1998). The role of scientific institutions in the promotion of biotechnology to the public (school, the mass‐media, entrepreneurs etc). Biochemical Education, 26(1), 52-55.
  • Panchin, A. Y., Aleoshin, V. V., & Panchin, Y. V. (2019). From tumors to species: a SCANDAL hypothesis. Biology direct, 14(1), 3.
  • Robertson, R. (2015). The discovery of cyclin: the unknown and the unknowable. On Biology https://blogs.biomedcentral.com/on-biology/2015/08/21/discovery-cyclin-unknown-unknowable/
  • Seluanov, A., Gladyshev, V. N., Vijg, J., & Gorbunova, V. (2018). Mechanisms of cancer resistance in long-lived mammals. Nature Reviews Cancer, 1.
  • Shahab, L., McGowan, J. A., Waller, J., & Smith, S. G. (2018). Prevalence of beliefs about actual and mythical causes of cancer and their association with socio-demographic and health-related characteristics: Findings from a cross-sectional survey in England. European Journal of Cancer, 103, 308-316.
  • Sprinzak, D., Lakhanpal, A., LeBon, L., Garcia-Ojalvo, J., & Elowitz, M. B. (2011). Mutual inactivation of Notch receptors and ligands facilitates developmental patterning. PLoS computational biology, 7(6), e1002069.
  • Tyson JJ, Chen K, Novak B. Network dynamics and cell physiology. Natl Rev Mol Cell Biol. 2001;2(12):908–916. doi: 10.1038/35103078.
  • Weiss, R. A., & Vogt, P. K. (2011). 100 years of Rous sarcoma virus. Journal of Experimental Medicine, 208(12), 2351-2355.
  • Werner, B., Traulsen, A., & Dingli, D. (2016). Ontogenic growth as the root of fundamental differences between childhood and adult cancer. Stem Cells, 34(3), 543-550.