Table 2.

Targeting brain-body-tumor crosstalk: current therapeutics and research landscape

Tumor type	Therapy	Target	Phase	Actual or target accrual	Primary endpoint	Status	Outcome	Reference
H3K27M spinal cord glioma	ONC201	DRD2/DRD3 antagonist	Phase 2	84	Progression-free survival	Terminated	8 of 12 patients alive at < 12 months median follow-up	NCT02525692
H3K27M diffuse midline glioma	ONC201	DRD2/DRD3 antagonist	Phase 2	95	Objective response rate	Ongoing	Not reported	NCT03295396
Neuroendocrine tumours	ONC201	DRD2/DRD3 antagonist	Phase 2	30	Tumour response	Completed	56% progressed	NCT03034200
Paediatric diffuse intrinsic pontine glioma	ONC201	DRD2/DRD3 antagonist	Phase 1	134	Recommended phase 2 dose	Terminated	Not reported	NCT03416530
Endometrial cancer	ONC201	DRD2/DRD3 antagonist	Phase 2	27	Progression-free survival	Terminated	Not reported	NCT03485729
Ovarian, fallopian tube, or primary peritoneal cancer	ONC201	DRD2/DRD3 antagonist	Phase 2	62	Dose-limiting toxicity, adverse events, objective response rate, progression-free survival	Ongoing	Not reported	NCT04055649
Recurrent and rare CNS tumours	ONC206	DRD2 antagonist	Phase 1	102	Dose-limiting toxicity	Ongoing	Not reported	NCT04541082
Paediatric high-grade glioma	INCB7839	ADAM10/17 inhibitor	Phase 1	13	Adverse events	Completed	Not reported	NCT04295759
Glioblastoma	Talampanel	AMPAR regulator	Phase 2	72	Overall survival	Completed	Improved overall survival compared with historical controls	NCT00943826, NCT00689221, NCT00813943, NCT00884741
Glioblastoma	Memantine	NMDAR regulator	Phase 2	4	Overall survival	Terminated	Not reported	NCT01260467
Glioma	Talampanel	AMPAR inhibitor	Phase 2	30	Progression-free survival	Terminated	Early termination due to futility	NCT00062504
Ovarian, primary peritoneal, or fallopian tube cancer	Propranolol, chemotherapy	β-adrenergic antagonist	Phase 1	32	Feasibility	Completed	Not reported	NCT01504126
Ovarian cancer	Propranolol	β-adrenergic antagonist	Phase 1	24	Feasibility	Completed	Improved quality of life	NCT01308944
Pancreatic cancer	Propranolol etodolac	β-adrenergic antagonist/COX-2 Inhibitor	Phase 2	210	Recurrence	Ongoing	Not reported	NCT03838029
Pancreatic cancer	Bethanechol	Muscarinic agonist	Phase 1	17	Change in Ki-67	Ongoing	Not reported	NCT03572283
Cancer pain	Tanezumab	Antibody against NGF	Phase 3	156	Change in pain	Completed	Not reported	NCT00545129 NCT02609828
Cancer pain	Resiniferatoxin	Capsaicin analogue	Phase 1	45	Safety	Ongoing	Not reported	NCT00804154
Melanoma	Propranolol, pembrolizumab	β-adrenergic antagonist	Phase 1	47	Safety	Completed	No dose-limiting toxicity; objective response rate 78%	NCT03384836
Bladder cancer	Propranolol, pembrolizumab	β-adrenergic antagonist	Phase 2	24	Objective response rate	Ongoing	Not reported	NCT04848519
Gastrointestinal Neuroendocrine Neoplasms	Somatostatin Analogs	Somatostatin Analogs	unknown	156	Adverse events	Completed	Not reported	NCT02788565
Prostate cancer	Carvedilol	β-adrenergic antagonist	Phase 2	22	Changes in serum PSA	Ongoing	Not reported	NCT02944201