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Cancer Development
Schematic
Development of
Metastatic
Cancer
What is Cancer?
Cancer or malignant neoplasm is the name given to a collection of related diseases, including
but not limited to breast cancer, lung cancer, prostate cancer, leukemia (cancer in the blood), etc. In
all types of cancer, the main similarity is that some of the body’s cells begin to divide without
stopping and spread into surrounding tissues. Due to its large spectrum of diseases, the chances of an
individual having cancer is high; one in two men and one in three women are diagnosed with cancer.
It is a result of a long process that begins when one of the cells in an organ or tissue becomes
damaged or altered in a way that causes it to break free from the normal controls that allow our cells
to work together in harmony. There are many aspects to cancer; When cancer develops cells become
more and more abnormal, old or damaged cells survive when they should die, and new cells form
when they are not needed. These extra cells can divide without stopping and may form growths called
tumors. Many cancers form solid tumors, which are masses of tissue. Cancers of the blood, such as
leukemia, generally do not form solid tumors. Not all tumors are cancerous, only malignant tumors
are. A malignant tumor has the ability to spread into, or invade, nearby tissues while a benign tumor
does not have these abilities. Benign tumors can sometimes be quite large, however. When removed,
they usually don’t grow back, whereas malignant tumors sometimes do.
Mutation
• Metastatic Cancer: A cancer that has spread from the primary site to other distant or local parts of the body.
• Occurs when cancer cells break away from a tumor and travel to other areas of the body through the
bloodstream or the lymph system.
• EMT, Epithelial Mesenchymal Transition: Transition that epithelial cells undergo in order to migrate away
from the primary site.
• EMT induces a decrease in cell contact inhibition and in adhesive characteristics of the malignant
epithelial cell.
• The reduced adhesiveness of cancer cells also results in morphological and cytoskeletal alterations
• “Many tumor cells are rounder than normal, in part because they are less firmly attached to either
the extracellular matrix or neighboring cells” (Cooper GM, 2016).
• Different types of EMT exist:
• Type 1 is “associated with implantation, embryo formation, and organ development”
• Type 2 is “associated with wound healing, tissue regeneration, and organ fibrosis,”
• “Type 3 EMT’s occur in neoplastic cells that have previously undergone genetic and epigenetic changes”
(Kalluri, 2009).
• The transition that cancerous epithelial cells undergo to become mesenchymal cells is type 3 EMT
• During type 3 EMT which cell adhesion molecule E-cadherin expression is decreased and N-cadherin and
vimentin expression is increased.
• When a cell becomes malignant TGF-β becomes and oncogene and promotes EMT and metastasis
Non-cancerous conditions
Normal Cell division is monitored at three checkpoints during the cell
division process:
G1 Checkpoint
G2 Checkpoint
M checkpoint
Every phase in the cell cycle is also regulated by various proteins at the
checkpoints. Cyclin dependent kinases, CDKs, along with various cyclins, are
the key proteins that regulate the cell cycle. When Cyclins bind to CDKs, the
CDKs become activated, allowing them to phosphorylate other molecules
and the process to proceed.
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Current Treatments
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Surgery:
Cryosurgery
Lasers
Hyperthermia
Photodynamic Therapy
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Radiation Therapy:
External Beam Radiation Therapy
Internal Radiation Therapy
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Immunotherapy:
Monoclonal antibodies
Adoptive cell transfer
Cytokines
Treatment Vaccines
BCG
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Targeted Therapy:
Small-molecule drugs
Monoclonal antibodies
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Hormone Therapy
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Stem Cell Transplant:
Autologous
Allogeneic
Syngeneic
Chemotherapy
Density dependent inhibition
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Presence of
adhesion
molecules
such as ECadherin
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Transmission electron microscopy of mesenchymal
(MES) and epithelial (E) cells
Future Treatments
Autocrine Growth Stimulation
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Contact Inhibition
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Immunohistochemistry of E-cadherin and vimentin expression
Immunohistochemistry of E-cadherin
and N-Cadherin expression
Causes of Cancer
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Precision Medicine
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Immunotherapy: White Blood Cell Armies
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Cell-Based Therapy: “Living Drugs”
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Epigenetic Therapy
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Research into Metastasis
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Knudsen's Hypothesis, also known as the “Two-Hit
Hypothesis”: The Two Hit Hypothesis states that cancer is
developed due to multiple mutations at different times.
“ Hits” can be:
• Acquired mutations
• External Mutations from :
• Carcinogens
• Radiation
• Viruses
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A- Strong E-Cadherin
C- Negative N-Cadherin
B- Benign Tumor
D- Strong E-cadherin
Immune system’s role
against cancer
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Cancerous Conditions
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Cell cycle checkpoints stop working
Loss of density dependent inhibition
Loss of contact inhibition
Uncontrollable cell division and proliferation
Loss of tumor suppressor genes and proto-oncogenes
Increase in oncogenes
Autocrine growth stimulation
Reduced expression of cell surface adhesion molecules like ECadherin
References
The Body’s response against
cancer utilizes the process of
immunoediting.
Immunoediting is a three step
process:
1. Elimination
2. Equilibrium
3. Escape
Contact Inhibition
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Density dependent inhibition
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https://www.goconqr.com/en/p/64884-dna-and-cell-division-notes
http://gleesonbiology.pbworks.com/f/1159269703/Cell%20cycle%20check%20points.jpg
Cooper GM. The Cell: A Molecular Approach. 2nd edition. Sunderland (MA): Sinauer Associates;
2000. The Development and Causes of Cancer. Available from:
http://www.ncbi.nlm.nih.gov/books/NBK9963/
4. Shook D, Keller R. Mechanisms, mechanics and function of epithelial-mesenchymal transitions in early
development. Mech Dev. 2003;120(11):1351–83.
5. Johansson J, Tabor V, Wikell A, Jalkanen S and Fuxe J (2015) TGF-β1-induced epithelial–
mesenchymal transition promotes monocyte/macrophage properties in breast cancer
cells. Front. Oncol. 5:3. doi: 10.3389/fonc.2015.00003
6. W.W. Minuth, L. Denk (2014). Advanced fixation for transmission electron microscopy unveils
special extracellular matrix within the renal stem/progenitor cell niche. Methods Mol Biol.
7. http://www.nature.com/nri/journal/v6/n11/fig_tab/nri1961_F1.html
8. http://www.riversideonline.com/source/images/image_popup/c7_cells.jpg
9. https://www.premedhq.com/loss-of-cell-cycle-control-in-cancer-cells
10. Imaging, Diagnosis, Prognosis:A Switch from E-Cadherin to N-Cadherin Expression Indicates Epithelial
to Mesenchymal Transition and Is of Strong and Independent Importance for the Progress
of
Prostate Cancer; Karsten Gravdal,Ole J. Halvorsen, Svein A. Haukaas, and Lars A. Akslen; Clin
Cancer Res December 1, 2007 13:7003-7011; doi:10.1158/1078-0432.CCR-07-1263
11. http://www.cancer.gov/about-cancer/treatment/types
12. https://www.mskcc.org/blog/future-five-reasons-optimism
The process of
immunoediting uses the
bodies immune system to
fight against the neoplastic
cells. Neoplastic cells are
cells that have been mutated
and are beginning to grow
abnormally.
13. http://www.moderncancerhospital.com/cancer-treatments/biological-immunotherapy/
14. Chen, Q.W., Zhu, X.Y., Li, Y.Y., & Meng, Z.Q. (2014). Epigenetic regulation and cancer (Review).
Oncology Reports, 31, 523-532. http://dx.doi.org/10.3892/or.2013.2913
15. http://www.carlagoldenwellness.com/2015/08/17/how-to-disease-proof-your-health/
16. Chakraborty, S., & Rahman, T. (2012). The difficulties in cancer treatment.Ecancermedicalscience, 6, ed16.
http://doi.org/10.3332/ecancer.2012.ed16
17. Escamilla, J. (2012, December 11). How immune cells can promote cancer progression - Sanguine Bio
Researcher Blog. Retrieved January 20, 2016, from http://technical.sanguinebio.com/how-immunecells-can-promote-cancer-progression/
18. Kalluri, R., & Weinberg, R. A. (2009). The basics of epithelial-mesenchymal transition. The Journal of
Clinical Investigation, 119(6), 1420–1428. http://doi.org/10.1172/JCI39104
19. Paul, S., Kuo, A., Schalch, T., Vogel, H., Joshua-Tor, L., McCombie, W. R., … Mills, A. A. (2013). Chd5
Requires PHD-mediated Histone 3 Binding for Tumor Suppression. Cell Reports, 3(1), 92–102.
http://doi.org/10.1016/j.celrep.2012.12.009
20. Snook, A. E., & Waldman, S. A. (2013). Advances in Cancer Immunotherapy.Discovery Medicine, 15(81),
120–125.
21. The Genetics of Cancer. (2012, March 26). Retrieved January 20, 2016, from
http://www.cancer.net/navigating-cancer-care/cancer-basics/genetics/genetics cancer
22. "Understanding Genetics." Understanding Genetics. The Tech Museum of Innovation, n.d. Web.23 Jan. 2016.
13. "What Is Cancer?" What Is Cancer? Cancer Center, 01 Jan. 0001. Web. 23 Jan. 2016.
Acknowledgements
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SUNY Old Westbury Honors College
Honors College Mentor : Dr. Anthony Deluca
Biology Mentor: Dr. Shilpi Paul