Guest Lecture: Protein and Cancer

Question 1

muscle protein balance

Answer 1

• synthesis = breakdown
• anabolism: synthesis > breakdown
• catabolism: synthesis < breakdown

Question 2

regulators of protein synthesis

Answer 2

• 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

Question 3

regulators of protein breakdown

Answer 3

• 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

Question 4

What is the RLS in protein synthesis?

Answer 4

Leucine so really need to make sure we get it

Question 5

How do we measure muscle?

Answer 5

• DEXA
• CT scans

Question 6

Application of CT scans

Answer 6

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

Question 7

How is muscle protein balance affected by cancer?

Answer 7

on average lose but is opportunity for protein synthesis

Question 8

How does cancer associated muscle change correlate with age related muscle change?

Answer 8

• 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

Question 9

Why is protein loss particularly bad in pancreatic cancer?

Answer 9

pancreas plays a major role in synthesis

Question 10

Why is protein loss particularly bad in pancreatic cancer?

Answer 10

pancreas plays a major role in synthesis

Question 11

Why does muscle change matter to a person recieving cancer treatment?

Answer 11

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

Question 12

Survival of patients with muscle loss vs no loss, advanced pancreatic cancer

Answer 12

Question 13

Causes of muscle loss in cqncer

Answer 13

• 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

Question 14

Causes of reduced food intake

Answer 14

• 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

Question 15

If we meet energy and protein requirements, can we prevent muscle loss in cancer?

Answer 15

No but it can be slowed down, causes for muscle loss in cancer is mainly due to cachexia

Question 16

describe cancer cachexia

Answer 16

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

Question 17

What reduced food intake is unique to cachexia?

Answer 17

tumour-induced, CNS-driven loss of appetite
* always feels like they just ate a massive thanksgiving dinner

Question 18

What happens with systemic inflammation with cachexia?

Answer 18

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

Question 19

What occurs with tumour-induced catabolism in cachexia?

Answer 19

• tumours secrete molecules that directly elicit catabolism

Question 20

How does treatment contribute to cachexia

Answer 20

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

Question 21

potential therapeutics

Answer 21

• theropeutic diet counselling
• branched chain amino acids
• possible role of creatine, carnitine, glutamine and arginine
• multi-modal therapeutics
• enobosarm oral drug
• anamorelin oral drug

Question 22

Therapeutic targets under investigation

Answer 22

• reduce inflammation
• provide adequate nutrients
• stimulate synthesis
• inhibit breakdown

Question 23

muscle loss in cancer results from?

Answer 23

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

Question 24

What is essential to the study and treament of cachexia?

Answer 24

a mutli-disciplinary team
* nutrition
* symptom management
* pharmaceuticals
* physiotherapy