Week 10 - cancer

Question 1

Evidence is emerging from murine studies showing that exercise training:

Answer 1

1) Controls cancer progression through direct effects on tumour intrinsic factors (growth rate, metastasis, tumour metabolism, and immunogenicity of the tumour),
2) Regulates tumour growth through interplay with systemic factors
3) Alleviates adverse events related to cancer and its treatment
4) Improves cancer treatment efficacy.

Question 2

Tumor growth kinetics and tumor formation

Answer 2

The control of tumour growth by exercise training in established tumours may be as high as a 67% reduction in growth rate but exercise in itself is not capable of directly eradicating tumours.

The Hippo signalling pathway (implicated in tumour formation) has been demonstrated to be downregulated by exercise.
- Exercise at intensities associated with increases in catecholamine levels can reduce the ability of cancer cells to form tumours in distant tissues, e.g., through regulation of the Hippo signalling pathway.

Question 3

Pre-incubation of cancer cells with exercise-conditioned serum more than halves tumor incidence when tumor cells are injected into sedentary mice

Answer 3

Thus, exposure to exercise-induced molecular factors may interfere with molecular signalling events in the cancer cells that are involved in tumor formation.

Question 4

Tumours from exercise animals had a much denser infiltration of immune cells; T cells, B cells, dendritic cells, and NK cells.

Answer 4

NK cells are known to be capable of killing cancer cells.
- They normally function to clear virus infected, stressed, or transduced cells.
The most sensitive immune cell type to acute exercise is the NK cell, which are mobilized within minutes of exercise. Maximal mobilization of NK cells is achieved after 30 min of exercise, and the max level of NK cells can be maintained up to 3hrs by continued training.

High cytotoxic activity in peripheral blood lymphocytes was linked to a lower cancer risk, suggesting that NK cells play a role in early tumour detection

Question 5

The exercise associated mobilization of NK cells can be mimicked by administration of epinephrine.

Answer 5

• Epinephrine is a key molecule in the exercise associated improved tumour control by cells of the immune system.

Question 6

Exercise is associated with the release of myokines from the contracting muscles.

Answer 6

One of the key myokines is interleukine-6 (IL-6).
- During exercise, the plasma level of IL-6 increases rapidly in an intensity-dependent manner.
IL-6 increases the mobilization of NK cells
Cancer cells often produce high levels of IL-6, which may help guide NK cells that have the IL-6 receptor to the tumour site.

Question 7

Exercise could represent a suitable combination partner to immune therapy in cancer patients

Answer 7

Facilitating improved response rates and more frequent complete lasting responses.
Moreover, exercise may directly—as a key component of a healthy lifestyle—delay or prevent tumour development