Cachexia and pancreatic cancer: Are there treatment options?

Table 1 Dietary supplements in the treatment of cancer cachexia

Agent	Mechanism of action	Ref.
N3-fatty acids (EPA, DHA, fish oil)	Reduction of pro-inflammatory cytokines and acute-phase-response	[32-36]
L-Carnitine	Antioxidant, cofactor of mitochondrial production of Acetyl-coA (ß-oxidation, aminoacid metabolism)	[37-40]
Antioxidants (GSH, ALA, NAC, vitamins A/C/E)	Reduction of ROS-formation and oxidative stress	[42-45]
Branched-chain-amino acids	Anabolic effects, stimulation of appetite and food intake	[46-49]
Lactoferrin	Increase of hemoglobin in anemic patients, iron-metabolism, decrease of inflammatory response	[50]

EPA: Eicosapentaenoic acid; DHA: Docosahexaenoic acid; GSH: Glutathione; ALA: Alpha-lipoic acid; NAC: N-acetyl-cysteine.

Table 2 Pharmacological treatment approaches for cancer cachexia

	Agent	Mechanism of action	Ref.
Potentially effective therapies	Progesterone	Appetite stimulation through neuropeptide y	[59,61,90-92]
	(MA, MPA)	down-regulation of pro-inflammatory cytokines
	Corticosteroids	Inhibition of prostaglandin activity, suppression of IL-1 and TNF-α	[62]
	Anabolic androgens	Muscle anabolism, up-regulation of protein synthesis, dose-dependent alterations of Akt-phosphorylation, GLUT-4 and ISR-expression	[64,65]
	SARMs	Selective modulation of androgen receptors in muscle tissue only	[67-69]
Experimental therapies	NSAIDs	Inhibition of COX-1 and -2 prostaglandin-synthesis, decrease of inflammatory reaction	[71,72]
	COX-2 selective inhibitors	Inhibition of prostaglandin-synthesis, decrease of inflammatory reaction, additional antineoplastic and anti-angiogenetic effects	[70,73,92]
	Thalidomide	Inhibition of TNF-α, and other pro-inflammatory cytokines, NF-κB, inhibition of COX-2	[74-76]
	Anti-TNF mAb	Inhibition of TNF-α	[78,79]
	Anti-IL-6 mAb	Inhibition of IL-6	[85]
	ACE-Inhibitors	Inhibition of angiotensin converting enzyme, role in cancer cachexia not yet fully understood	[88,89]
	Myostatin-inhibitors/ActIIrb-antagonists	Inhibition of ActIIrb signaling, stimulation of muscle growth and regeneration	[4,66,86,87]
	Ghrelin/Ghrelin mimetics	Stimulation of GH-secretion, appetite stimulation though neuropeptide y, decrease of sympathetic nerve activity	[54-57]
	Mirtazepin, Olanzapine	Appetite stimulation through serotonergic blockade	[58,59]
Treatments without proven effectiveness	Pentoxifylline	Inhibition of TNF-α	[77]
	Insulin, IGF-1, GH	Regulation of body composition (fat, glucose and protein metabolism) via PI3K/Akt-, MAPK-pathways	[63,64,95]
	Cannaboids (dronabinol)	Appetite stimulation, energy hemostasis	[53]

MA: Megestrol acetate; MPA: Medroxyprogesterone acetate; COX-2: Cyclooxygenase-2; SARMs: Selective androgen receptor modulators; NSAIDs: Non-steroidal anti-inflammatory drugs; TNF: Tumor necrosis factor; IL: Interleukin; IGF: Insulin-like growth factor; GH: Growth hormone; GLUT-4: Glucose transporter-4; ISR: Induced systemic resistance; MAPK: Mitogen-activated protein kinase.