Testicular Cancer/Metastatic Process

Question 1

What is the leading cause of treatment failure in cancer patient?

Answer 1

Metastatic disease

Question 2

What are the 7 steps of the metastatic cascade?

Answer 2

1. Growth of primary tumor
2. Angiogenesis at primary tumor site
3. Local invasion
4. Detachment and embolization
5. Arrest in distant organ capillary beds
6. Extravasation
7. Proliferation

Question 3

Explain the process of angiogenesis at the primary tumor site

Answer 3

cancer cells, as all other cells, require oxygen and nutrients in order to grow. Tumor cells release angiogenic factors to stimulate the development of new capillary beds at the tumor site, which provides tumors with the nutrients they need to continue to grow

Question 4

How does local invasion of a tumor occur?

Answer 4

Mechanical pressure forces projections of cancer cells into adjacent tissue through basement membranes, increased cell motility contributes along with lack of adhesion of cancer cells so cells can escape and tumour cells secrete enzymes that can destroy basement membranes.

Question 5

What is detachment and embolization?

Answer 5

< 0.01% of the millions of tumour cells that are shed, are successful in forming metastatic lesions. On entering the circulation, tumour cells face destruction by the immune system, so for protection they clump with blood cells, particularly platelets, to form emboli and enhances their ability to adhere to capillary walls in target organs.

Question 6

What is organ tropism?

Answer 6

When cancers show a preference for a specific organ when metastasizing.

Question 7

What does extravasation refer to in the metastatic process?

Answer 7

Once the tumour cells are firmly attached to the vessel wall, they must extravasate (penetrate) through the wall to grow into the extravascular tissue. They use the same process as they used to initially enter the vascular system. Once the damage is done, tumour cells escape and invade the tissue.

Question 8

Why is proliferation an important step in the metastatic process?

Answer 8

Once the tumour cells arrive in the tissue they require a blood supply and nutrients. The new environment may be very different therefore the cells need to adapt to the new environment. Poorly differentiated cancer cells generally adapt better.

Question 9

What are the 4 most common sites of metastatic disease?

Answer 9

LIVER
LUNG
BONE
CNS

Question 10

Define osteolysis

Answer 10

the process of destruction of old and damaged bone.

Question 11

Osteoclasts are responsible for…….

Answer 11

resorption of bone products once stimulated by the growth factors released in osteolysis

Question 12

What are osteoblasts responsible for?

Answer 12

generating new bone matrix

Question 13

Why are bone mets so difficult to treat?

Answer 13

because it is a vicious compensatory cycle. Resorption by osteoclasts occurs in response to the breakdown of bone in osteolysis. Resorption then stimulates the release of growth factors to stimulate regrowth of area of bone breakdown. Since the tumor is surrounding the area of bone breakdown, the presence of growth factors that increases the action of osteoblasts can ALSO stimulate tumor growth.

Question 14

What is the role of biphosphonates in the treatment of bone metastasis?

Answer 14

help draw calcium out of the blood vessels back into the bones to try and reduce the rate and risks of skeletal complications