carcinogenenesis

Question 1

Name 6 hallmarks which will transform normal cells into cancer cells

Answer 1

1. Sustaining proliferative signaling
2. Evading growth suppressors
3. Resisting cell death
4. Enabling replicative immortality
5. Inducing angiogenesis
6. Activating invasion and metastasis

Question 2

List therapeutic targets for three of the hallmarks and justify why you would want to activate or inhibit these targets to reduce the onset of cancer

Answer 2

• Inhibit Telomerase, is expressed in cancer cells to extend telomeric DNA, enabling replicative immortality
• Inhibit VEGF-A, encodes ligands involving in orchestrating the growth of new blood vessels, inducing angiogenesis.
• Upregulate E-cadherin, cell-to-cell adhesion molecule, which is inactivated or downregulated in cancer cells, to activate invasion and metastasis.

Question 3

What is angiogenesis and why does a tumor need this to thrive

Answer 3

Angiogenesis causes normally quiescent vasculature to continually sprout new blood vessels that help sustain expanding neoplastic growth, by proving tumors with a way of delivering sustenance (nutrients and oxygen) and getting rid of metabolic wastes and carbon dioxide.

Question 4

Which cell types are present in the tumor microenvironment and indicate for two how they regulate tumor growth

Answer 4

• Cancer cells; ‘normal’cancer cells, invading/migrating cancer cells, cancer stem cells
• Non-cancer cells; endothelial cells, fibroblasts, immune cells, stem cells
• Secreted soluble factors; Cytokines, chemokines, growth factors, proteases
• Non cellular solid material; ECM

Endothelial cells in the tumor microenvironment are activated by cancer cells to construct new blood vessels (angiogenesis), needed for tumor maintenance and growth

Growth factors support tumor growth, eg TGF-beta (inhibits growth) which often is mutated in tumors or tumors are less affected, is also secreted by tumors to suppress growth in neighboring cells, aiding in rapid reproduction without competition of the neighboring cells.

Question 5

name 2 of the 6 original cancer hallmarks and explain how they cause cells to become cancerous

Answer 5

• Sustaining proliferative signaling: deregulation of growth-promoting signals, causes cancer cells to grow when ‘normal’ cells would not be instructed to do so. eg by increasing the amount of growth facto receptors, causing the cell to become hyperresponsive to otherwise limiting amounts of growth factor ligands.
• Resisting cell death: attenuation of apoptosis in tumors, apoptosis serves as a natural barrier to cancer development. eg by loss of TP53 tumor suppressor function, the cell remains alive even though the cell has critical damage.

Question 6

What does the term ‘self-sufficiency’ in growth signals mean in cells and describe two manners in which this can take place

Answer 6

The ability of cancer cells to grow without external stimulation to do so. By permanently activating the pathways that respond to these signals, or by destroying the ‘off-switches’ that prevent excessive growth form these signals. (or autocrine signaling).

Question 7

Describe the warburg effect

Answer 7

Energy production in cancer cells by less efficient aerobic glycolysis. Taking up large amounts of glucose, producing mostly lactate and only a small amount of energy. (4 mol ATP/glucose instead of 36 mol ATP/glucose in oxidative phosphorylation). Many of the remaining carbon atoms derived from glucose are diverted for use as raw materials for synthesis of the proteins, nucleic acids and lipids required for tumor growth.