1.6 Principles of Oncogenesis

Question 1

What is the etiology of cancer?

Answer 1

(1) genetic factors

• heritable gene mutations can increase cancer susceptibility
• mucations can be directly inherited or acquired (random vs environmental insults)

(2) breed dispositions

• boxers: lymphoma, MCT
• giant breeds, e.g., irish wolfhounds: osteosarcoma
• GSD: hemangiosarcoma
• flat coat retrievers: soft tissue sarcomas

(3) hormonal factors

• female: estrogen and progesterone (mammary tumors)
• male: androgens (prostate carcinoma / perianal adenoma)

(4) environmental factors

• exposure to damaging agents (US, viruses, carcinogens)

Question 2

What are proto-oncogenes vs tumor supressor genes?

Answer 2

proto-oncogenes (growth factors, GFr, transcription factors, etc):

• genes whose normal function is to promote cell growth, proliferation, or inhibit apoptosis
• with loss of control it becomes an oncogene
• some viruses contain oncogenes

tumor supressor genes (p53, retinoblastoma protein):

• act to prevent uncontrolled proliferation (activate apoptosis)
• downregulation can lead to oncogenesis

Question 3

How does mutagenesis contribute to cancer?

Answer 3

mutations in key genes contribute to cancer; 10-12 mutations must occur in one cell before it may develop into a clinically significant cancer

• gain of function mutations (oncogenes)
• loss of function mutations (tumor supressor genes)
• insertion/deletion/missense
• chromosomal rearragements

Question 4

What are the hallmarks of successful cancers?

Answer 4

1. sustaining proliferative signaling
2. evading growth suppressors
3. resisting cell death
4. enabling replicative immortality (avoiding senescence)
5. inducing angiogenesis
6. tissue invasion and metastasis
7. avoiding immune destruction
8. tumor promoting inflamamtion