Ch 316 - Tumor biology

Question 1

What are the 8 hallmarks of cancer proposed by Hanahan and Weinberg

Answer 1

1. Sustained angiogenesis
2. Evading apoptosis
3. Self-sufficiency in growth signals
4. Insensitivity to anti-growth signals
5. Tissue invasion and metastasis
6. Limitless replicative potential
7. Deregulating cellular metabolism
8. Immune evasion

Question 2

What is the difference in alleles between oncogenes and tumor suppressor genes?

Answer 2

• Oncogenes: Activation requires mutation in only ONE allele (dominant event)
• Tumor suppressor genes: Require loss of BOTH alleles (recessive event)

Question 3

What is the primary function of the P53 gene, and why is it significant in cancer?

Answer 3

• Acts as a “checkpoint gene” that surveys cellular DNA damage
• Stops cell division when significant DNA damage is detected
• Can trigger programmed cell death (apoptosis)
• Loss of P53 is the most common genetic alteration in human cancers
• Prevents potentially cancerous cells from continuing to divide

Question 4

Explain the “two hits” concept in cancer genetics.

Answer 4

• Describes how two genetic events can lead to cancer development
• First “hit”: Often a hereditary risk factor
• Second “hit”: A sporadic genetic event
• Explains why some families have increased cancer risk

Question 5

How does telomerase contribute to cancer cell immortality?

Answer 5

• Telomeres normally shorten with each cell division
• Telomerase extends telomere length, preventing cellular aging
• Cancer cells have high telomerase activity
• Provides limitless replicative potential to cancer cells

Question 6

What are the 5 key steps in the metastatic cascade?

Answer 6

1. Cellular basement membrane invasion and migration
2. Invasion of nearby vessels and lymphatics
3. Survival in circulation
4. Extravasation into new tissues
5. Proliferation in new site

Question 7

What is angiogenesis, and how does it differ from vasculogenesis?

Answer 7

• Angiogenesis: Formation of new blood vessels within existing tissue
• Vasculogenesis: Formation of blood vessels de novo during embryogenesis
• Driven by hypoxia and growth factors like VEGF and PDGF
• Critical for tumor growth and potential metastasis

Question 8

What is epigenetics, and how does it relate to cancer development?

Answer 8

• Changes in gene function without altering DNA sequence
• Involves modifications to regulatory elements like gene promoters
• Can be more common in cancer than direct genetic mutations
• Closely linked to environmental and acquired cancer risks

Question 9

What are cancer stem cells (CSCs), and why are they important?

Answer 9

• Small population of cells within a tumor
• Ability to self-renew and generate new tumor cells
• Resistant to conventional treatments
• Can cause cancer recurrence and metastasis
• Potential target for novel cancer therapies

Question 10

What is Toceranib’s mechanism of action?

Answer 10

• Receptor tyrosine kinase (RTK) inhibitor developed to target c-kit in mast cell tumors.
• Also inhibits the RTKs of VEGF, and other proteins, involved in angiogenesis with activity against a number of cancer types, independent of c-kit.