Lecture 31 - Cancer cachexia Flashcards
What is cancer cachexia and the criteria for diagnosis?
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
cachexia affects >__% of cancer patients
80%
true or false
cancer cachexia is more common in children and int he elderly, and becomes more pronounced as the cancer progresses
true
what are the consequences of cancer cachexia that lead to a decrease in quality of life?
reduced muscle function
impaired mobility
enhanced fatigue
reduced independence
premature retirement
increased incidence of metabolic diseases
increased risk of complications during surgery
cachexia also impairs responces to _____ therapy and increases ______and ______failure
cachexia also impairs responces to chemo-radio therapy and increases respiratory and cardiac failure
The probability of remaining failure free in colorectal cancer are _____ with cachexia
decreased
as well as a decreased rate of survival following chemotherapy
The c-26 mouse model of cachexia is a good pre-clinical model.
what are the two types?
c-26 mild - mimicks the pre-cachexia stage
c-26 severe - mimicking the refractory cachexia stage
in c-26 severe, chemotherapy only reduced tumour size by __% as opposed to __% in c-26-mild
in c-26 severe, chemotherapy only reduced tumour size by 42% as opposed to 82% in c-26-mild
true or false
cadavers with cancer cachexia have reduced heart mass, structural remodeling and cardiac fibrosis
true
heart was full of collagen (fibrosis)
chemotherapy is associated with cardiotoxicity.
how does cachexia affect this
it increases the susceptibility to chemotherapy induced cardiac atrophy
Cachexia is responsible for __-__% of all cancer related deaths
Cachexia is responsible for 20-30% of all cancer related deaths
In cancer patients, muscle mass is a predictor of:
the toxicity associated with chemotherapy
the change of remaining failure free following chemotherapy;
survival
a 15% decrease in muscle mass =
25-30% decrease in muscle mass =
a 15% decrease in muscle mass = reduced function
25-30% decrease in muscle mass =death
true or false
muscle strength is also a predictor of survival
true
and tumour free
true or false
cachexia patients have a decrease in energy expendature
false
increase in resting energy expendature
true or false
cachexia patients will usually have a reduction in food intake
true
treatments for cachexia target which abnormalities?
metabolic alterations
increases in protein degradation
decreases in protein synthesis
decreases in membrane integrity
cytokine release
anorexia
does c-26, MoCR, LLC and PDA mouse models have all the features of human cachexia
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
In terms of anorexia treatment, although many successfully increase food intake, they have little effect on…
improving lean muscle mass or quality of life
what are the issues with drugs targeting the cytokines of cancer cachexia?
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
Myostatin inhibitory antibodies will have what effect?
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
What is activin A?
another member of the TGFb1 family, like myostatin
true or false
Activin A leads to more loss of muscle mass than myostatin
true
they both signal through the ACTRIIA/B receptor
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
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
Treatment with an ACE inhibitor did no improve body mass or muscle mass but did…
cause large improvements in muscle function and fatigue and corrected the metabolic alterations in mice with cancer cachexia
same results in mild/severe mouse
Treatment with an __ ______ _____ improved survival, prevented the loss in body mass and muscle mass and increase muscle strength in mice with cancer cachexia
Fn14 inhibitory antibody
stops the TWEAK ligand binding Fn14 receptor
What is a predictor of survival
the amount of muscle strength that is lost
what is a predictor of chemotherapy toxicity and response, in addition to survival?
the amount of reduction in muscle mass
true or false
combination therapy will be the best treatment for cancer cachexia
true
true or false
exercise is crucial to cancer survival
true - mostly (more studies need to be done)
reduces factors for protein breakdown etc…
many treatments showing promise in preclinical models have had little or no effect in clinical trials - what is the main reason?
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
what are future directions of cancer cachexia research?
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
