Lecture 31 - Cancer cachexia

Question 1

What is cancer cachexia and the criteria for diagnosis?

Answer 1

the multifacrtorial syndrome characterised by an ongoing loss of skeletal muscle mass with or without loss of fat mass that leads to progressive functiona impairment

can’t be reversed by nutritional changes

criteria:
weight loss >5% over th past 6 months

BMI 2%

appendicular skeletal msucle index consistent with sarcopenia

Question 2

cachexia affects >__% of cancer patients

Answer 2

80%

Question 3

true or false

cancer cachexia is more common in children and int he elderly, and becomes more pronounced as the cancer progresses

Answer 3

true

Question 4

what are the consequences of cancer cachexia that lead to a decrease in quality of life?

Answer 4

reduced muscle function

impaired mobility

enhanced fatigue

reduced independence

premature retirement

increased incidence of metabolic diseases

increased risk of complications during surgery

Question 5

cachexia also impairs responces to _____ therapy and increases ______and ______failure

Answer 5

cachexia also impairs responces to chemo-radio therapy and increases respiratory and cardiac failure

Question 6

The probability of remaining failure free in colorectal cancer are _____ with cachexia

Answer 6

decreased

as well as a decreased rate of survival following chemotherapy

Question 7

The c-26 mouse model of cachexia is a good pre-clinical model.

what are the two types?

Answer 7

c-26 mild - mimicks the pre-cachexia stage

c-26 severe - mimicking the refractory cachexia stage

Question 8

in c-26 severe, chemotherapy only reduced tumour size by __% as opposed to __% in c-26-mild

Answer 8

in c-26 severe, chemotherapy only reduced tumour size by 42% as opposed to 82% in c-26-mild

Question 9

true or false

cadavers with cancer cachexia have reduced heart mass, structural remodeling and cardiac fibrosis

Answer 9

true

heart was full of collagen (fibrosis)

Question 10

chemotherapy is associated with cardiotoxicity.

how does cachexia affect this

Answer 10

it increases the susceptibility to chemotherapy induced cardiac atrophy

Question 11

Cachexia is responsible for __-__% of all cancer related deaths

Answer 11

Cachexia is responsible for 20-30% of all cancer related deaths

Question 12

In cancer patients, muscle mass is a predictor of:

Answer 12

the toxicity associated with chemotherapy

the change of remaining failure free following chemotherapy;

survival

Question 13

a 15% decrease in muscle mass =

25-30% decrease in muscle mass =

Answer 13

a 15% decrease in muscle mass = reduced function

25-30% decrease in muscle mass =death

Question 14

true or false

muscle strength is also a predictor of survival

Answer 14

true

and tumour free

Question 15

true or false

cachexia patients have a decrease in energy expendature

Answer 15

false

increase in resting energy expendature

Question 16

true or false

cachexia patients will usually have a reduction in food intake

Answer 16

true

Question 17

treatments for cachexia target which abnormalities?

Answer 17

metabolic alterations

increases in protein degradation

decreases in protein synthesis

decreases in membrane integrity

cytokine release

anorexia

Question 18

does c-26, MoCR, LLC and PDA mouse models have all the features of human cachexia

Answer 18

only c-26, MoCR have all features

LLC- no decrease in muscle fibre size or premature death

PDA - unsure whether there is a decrease in muscle strength or increase in fatigue

Question 19

In terms of anorexia treatment, although many successfully increase food intake, they have little effect on…

Answer 19

improving lean muscle mass or quality of life

Question 20

what are the issues with drugs targeting the cytokines of cancer cachexia?

Answer 20

anti-inflammatory drugs have often been associated with adverse side effects

another limitation is that they usually only target one cytokine

New drugs are being produced to target several cytokines simultaneously and are showing beneficial effects for muscle mass and function

Question 21

Myostatin inhibitory antibodies will have what effect?

Answer 21

decrease in myostain leads to hypertrophy

but treatment with Myostatin inhibitory antibodies caused small improvements in muscle mass and funciton in mice with cancer cachexia

Question 22

What is activin A?

Answer 22

another member of the TGFb1 family, like myostatin

Question 23

true or false

Activin A leads to more loss of muscle mass than myostatin

Answer 23

true

they both signal through the ACTRIIA/B receptor

Question 24

Treatment with soluble ______ receptor to prevent myostatin and activin binding caused large improvements in muscle mass and function, and prolonged survival in mice with cancer cachexia

Answer 24

Treatment with soluble activin receptor (ACTRIIA/B) to prevent myostatin and activin binding caused large improvements in muscle mass and function, and prolonged survival in mice with cancer cachexia

Question 25

Treatment with an ACE inhibitor did no improve body mass or muscle mass but did…

Answer 25

cause large improvements in muscle function and fatigue and corrected the metabolic alterations in mice with cancer cachexia

same results in mild/severe mouse

Question 26

Treatment with an __ ______ _____ improved survival, prevented the loss in body mass and muscle mass and increase muscle strength in mice with cancer cachexia

Answer 26

Fn14 inhibitory antibody

stops the TWEAK ligand binding Fn14 receptor

Question 27

What is a predictor of survival

Answer 27

the amount of muscle strength that is lost

Question 28

what is a predictor of chemotherapy toxicity and response, in addition to survival?

Answer 28

the amount of reduction in muscle mass

Question 29

true or false

combination therapy will be the best treatment for cancer cachexia

Answer 29

true

Question 30

true or false

exercise is crucial to cancer survival

Answer 30

true - mostly (more studies need to be done)

reduces factors for protein breakdown etc…

Question 31

many treatments showing promise in preclinical models have had little or no effect in clinical trials - what is the main reason?

Answer 31

a lack of standard and appropriate tests

preclinical tests need to be clinically relevant

clinical trials have been initiated without examining effects on fatigue, muscle function and survival

assessment of these aspects of cancer cachexia should be included as standard tests in preclinical trial

Question 32

what are future directions of cancer cachexia research?

Answer 32

combination therapies

the role of cachexia in modulating the response to chemotherapy

assessing treatment efficacy in different models and stages of cancer cachexia

cardiac cachexia - mechanisms and treatment

cachexia in obese populations