Table 5.

Recapitulation of recent clinical trials reporting effects on the neuroendocrine axis of melanoma.

Tested Substance	Study Type	Mechanism	Effect	Reference
β-blockers (metoprolol, propranolol, atenolol, and others)	Cohort study (4179 patients)	Blocking βARs	Increased survival in melanoma patients	[83]
β-blockers (unspecified)	Cohort study (121 patients)	Blocking βARs	Reduced risk of disease progression	[84]
β-blockers (pan or β1 selective)	Cohort study (195 patients)	Inhibition of stress signaling, particularly via β2AR signaling	Increased survival in melanoma patients	[86]
β-blockers (pan or β1 selective)	Cohort study (203 patients)	Blocking βARs	No impact on survival in melanoma patients	[91]
Riluzole	Phase 0 trial (12 patients)	Glutamate blockade inhibiting MAPK and PI3k/Akt signaling	Melanoma metabolic activity suppression was achieved. Inconsistent effects	[117]
Riluzole	Phase II trial (13 patients)	Inhibition of GRM1 signaling Increased leukocyte infiltration	Antitumoral biological effects. No tumoral response recorded according to staging criteria	[100]
Ipilimumab	Phase II trial (75 patients)	NO-mediated modulation of the tumor microenvironment	Mixed anti- and pro-melanoma activity. Inconsistent effects of NO and metabolites	[343]
SSRIs (unspecified)	Cohort study (5591 patients)	Inhibition of serotonin uptake	Decrease in survival of melanoma patients	[141]
Cannabis	Cohort study (140 patients)	Complex interaction with the immune response, possibly CB2-mediated	Decrease of response rate to nivolumab in patients with advanced melanoma	[153]
Pasireotide	Phase I trial (10 patients)	SSTRs-mediated Ras/MAPK signaling modulation	Stable disease and partial response were obtained. Progression of disease also recorded in some patients	[213]