Molecular therapeutic strategies targeting pancreatic cancer induced cachexia

Table 1 Cytokines involved in cachexia, function, and specific targeted therapies

Cytokine	Function	Drug
TGF-β	Decreases protein synthesis; increases muscle catabolism	Trabedersen (binds TGF-β mRNA)
TNF-α	Generates radical oxygen species; increases ubiquitin-proteasome activity	Infliximab (anti-TNF-α mAb); etanercept (recombinant TNF-αR); thalidomide/lenalidomide (inhibits TNF-α); pentoxifylline (inhibits TNF-α)
IL-6	Mediates systemic inflammation; increases muscle catabolism; regulates synthesis of acute phase reactants	Clazakizumab (anti-IL-6 mAb ); tocilizumab (anti-IL-6 receptor mAb)

TGF-β: Transforming growth factor-beta; IL-6: Interleukin-6; TNF-α: Tumor necrosis factor-alpha.

Table 2 Dietary changes and observed effects in pancreatic cancer induced cachexia

Ketogenic diet	Diminishes tumor growth and induces apoptosis
	Increases skeletal muscle mass
Silibinin	Inhibits IL-6, IL-8, TNF-α secretion
	Downregulates glycolysis proteins
	Increases skeletal muscle mass
ω3 Fatty acid	Regulates metabolic dysfunction
	Lowers IL-6, TNF-α, CRP
	Improves host immune response

IL-6: Interleukin-6; TNF-α: Tumor necrosis factor-alpha; CRP: C-reactive protein.