Guest Lecture: Protein and Cancer Flashcards
muscle protein balance
- synthesis = breakdown
- anabolism: synthesis > breakdown
- catabolism: synthesis < breakdown
regulators of protein synthesis
- resistance exercise (prolonged upregulation past 48 hrs)
- ingestion of high-quality protein (leucine/arginine signaling via mTOR)
- hormone signals (insulin, IGF-1, testosterone) to stimulate mTOR pathway
regulators of protein breakdown
- resistance exercise (rate returns to baseline after 48 hrs
- early starvation/ low EAA
- stress/injury/illness (inflammation): signaling cascades connected to autophagy genes and ubiquitin-proteosome pathway; cortisol, epinephrine, glucagon
What is the RLS in protein synthesis?
Leucine so really need to make sure we get it
How do we measure muscle?
- DEXA
- CT scans
Application of CT scans
can reveal abnormalities in muscles
* muscle mass correlates with cross-sectional area at L3 (cm2)
* intermuscular adipose tissue: marbling in the muscle
* mean muscle attenuation: lipid content inside muscle cells
How is muscle protein balance affected by cancer?
on average lose but is opportunity for protein synthesis
How does cancer associated muscle change correlate with age related muscle change?
- age associated muscle loss is estimated to be a gradual loss of muscle mass of 0.3% to 0.8% per year after middle age, up to 1% per year by age 75. Can potentially be overcome with greater volumes of resistance exercise or greater doses of protein.
- for cancer patients (especially pancreatic cancer) can be up to 30% in just 4 months
Why is protein loss particularly bad in pancreatic cancer?
pancreas plays a major role in synthesis
Why is protein loss particularly bad in pancreatic cancer?
pancreas plays a major role in synthesis
Why does muscle change matter to a person recieving cancer treatment?
May cause loss of tolerance for treatment because with chemo it has impact for about 2 weeks trying to knock out the rapid cell growth so need people to be able to recover quickly if losing a bunch of neutrophils and with less msucle mass they cannot keep up.
* treatment intolerance → increased infection → decreased function → decreased quality of life →living just to survive
Survival of patients with muscle loss vs no loss, advanced pancreatic cancer
Causes of muscle loss in cqncer
- Increased protein requirements for body cell repair/healing after radiation and cytotoxic chemo
- Elevated energy expenditure in some cases mostly at resting state
- tumour is a leech and wants all of the nutrients and you CANNOT starve it
- Altered absorption in some GI cancers
- reduced food intake
Causes of reduced food intake
- fatigue-loss of desire to eat
- side effects-altered/loss of taste
- knowledge-confusion around food for prevention vs. treatment
- financial-difficult to afford quality product
If we meet energy and protein requirements, can we prevent muscle loss in cancer?
No but it can be slowed down, causes for muscle loss in cancer is mainly due to cachexia
describe cancer cachexia
loss of skeletal muscle ± adipose tissue which cannot be reversed by nutrient provision, driven by a variable combination of:
* reduced food intake via treatment induced and/or tumour induced (CNS driven) loss of appetite
* altered metabolism elevating EE, increasing systemic inflammation and excess catabolism
What reduced food intake is unique to cachexia?
tumour-induced, CNS-driven loss of appetite
* always feels like they just ate a massive thanksgiving dinner
What happens with systemic inflammation with cachexia?
tumor or immune-mediated cytokine release to the liver (interleukin-6, interleukin-1, TNF) altering levels of acute phase proteins (increased c-reactive protein, decreased albumin) and leads to anorexia, insulin resistance, and muscle breakdown
What occurs with tumour-induced catabolism in cachexia?
- tumours secrete molecules that directly elicit catabolism
How does treatment contribute to cachexia
pro-inflammatory factors elicit catabolism
* targeted therapy: drugs that directly target mTOR pathway
* glucocorticoids used mainly for palliation of side effects, but high doses are given in
hematological malignancy
certain chemotherapies are platinum-based cytotoxic drugs
potential therapeutics
- theropeutic diet counselling
- branched chain amino acids
- possible role of creatine, carnitine, glutamine and arginine
- multi-modal therapeutics
- enobosarm oral drug
- anamorelin oral drug
Therapeutic targets under investigation
- reduce inflammation
- provide adequate nutrients
- stimulate synthesis
- inhibit breakdown
muscle loss in cancer results from?
reduced muscle protein synthesis AND increased breakdown
* Driven by a variable combination of reduced intake and altered metabolism
* Cannot be reversed solely by provision of adequate nutrients
* has significant impact on patient experience and treatment outcomes
What is essential to the study and treament of cachexia?
a mutli-disciplinary team
* nutrition
* symptom management
* pharmaceuticals
* physiotherapy
