Cancer Biology (Objectives Only)

What are some carcinogens and how do they contribute to cancer development?

- UV radiation → nasal planum and cutaneous squamous cell CA

- Ionizing radiation → sarcoma development in sites of previous radiation treatment

- Pesticides, herbicides, insecticides (Newer spot-on topical flea and tick products have not)

- Hormonal exposure

- Rural vs. urban environment

- Genetics (Cancer is a genetic disease, however it is not always heritable)

Bladder cancer is increased with what therapies, especially in overweight dogs?

- Topical insecticides and dips

What breeds are predisposed to TCC?

- Beagles (x3)

- Scotties (x21)

- Westies (x6)

What are the phases of carcinogenesis?

1) Initiation

2) Promotion

3) Progression

Describe the initiation phase of carcinogenesis.

- Interaction of the carcinogen with cellular DNA -> DNA damage may remain undetected (silent) for life unless further events stimulate the tumor development

True or false: initiation is reversible.

- True

True or false: An initiated cell is a cancer cell.

- False (not yet; Does not have autonomous growth ability)

Describe the promotion phase of carcinogenesis.

- Clonal expansion of the initiated cell (mutated genes give a selective growth advantage and produces lg. population of cells at risk for further genetic damage)

True or false: Tumorgenesis only requires the presence of a promoter.

- False; Tumors cannot develop if only the promoter is applied, or if promoter is applied before initiation occurs

Describe the progression phase of carcinogenesis.

- Tumor obtains ability to invade tissues and metastasize to distant locations

What are the hallmarks of the progression phase of carcinogenesis?

- Increased genetic instability

- Nuclear alterations

What are the 6 foundational hallmarks of cancer?

1) Sustaining proliferative signaling

2) Evading growth suppressors (i.e., Rb or P53)

3) Resisting cell death (i.e., loss of function of p53)

4) Inducing angiogenesis

5) Enabling replicative immortality

6) Activating invasion and metastasis

Cancer cells >________ from blood vessel become hypoxic.

- 2mm

What is angiogenic switch?

- Shift in balance between angiogenic factors and anti-angiogenic factors -> Induces formation of new vessels by recruiting progenitor cells, pericytes, smooth muscle cells

Most cancer-related deaths are due to primary neoplasia or metastasis?

- Metastasis

What are the 8 recent additional hallmarks of cancer?

1. Nonmutational epigenetic reprogramming

2. Avoiding immune destruction

3. Tumor promoting inflammation

4. Polymorphic microbiomes

5. Senescent cells

6. Genome instability and mutation

7. Deregulating cellular metabolism

8. Unlocking phenotypic plasticity

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What is the function of palladia?

- Tyrosine kinase inhibitor; Also inhibits angiogenesis

How does metronomic dosing of chemotherapy target the hallmarks of neoplasia?

- Aimed to slow progression of tumor through multiple mechanisms (angiogenesis, tumor immunology)