Table 1 Emerging interventions and drugs used in clinical trials for the treatment of patients with advanced disease or in preclinical PC models

PARP inhibitor

Olaparib

PROfound Study

CRPC with BRCA1/2 mutations

Phase III clinical trial

NCT02987543

Niraparib

Galahad

CRPC with DNA-Repair Anomalies

Phase II clinical trial

NCT02854436

Rucaparib

TRIUMPH

Metastatic Hormone-Sensitive PC with Germline DNA Repair Gene Mutations

Phase III clinical trial

NCT03413995

Rucaparib

ROAR

CRPC with BRCA gene alteration

Phase II clinical trial

NCT03533946)

Talazoparib

TALAPRO-1

CRPC with DNA Repair Defects

Phase III clinical trial

NCT03148795

Veliparib (ABT-888)

ABT-888

CRPC

Phase II clinical trial

NCT01085422

AR antagonists/inhibitors

JNJ-56021927(ARN-509; Apalutamide)

JNJ-56021927 effects on the Pharmacokinetics of Multiple Cytochrome P450 enzymes and transporter

CRPC

Phase I clinical trial

NCT02578797

Proxalutamide (GT0918)

Proxalutamide (GT0918) in Subjects With CRPC

CRPC

Phase II clinical trial

NCT03899467

Hedgehog inhibitors

Vismodegib

A Pharmacodynamic Study of Vismodegib

CRPC With Accessible Metastatic Lesions for Tumor Biopsy

Phase I clinical trial

NCT01880437

anti-PDCD1 and -CTLA-4 (IgG1κ) antibodies

Nivolumab + ipilimumab

INSPIRE

immunogenic CRPC

Phase II clinical trial

NCT04717154

anti-PD-L1 Antibody + AR antagonist

Atezolizumab + Enzalutamide

IMbassador250

CRPC after Failure of an Androgen Synthesis Inhibitor

Phase III clinical trial

NCT03016312

anti-PD-1 + anti-IL-8 antibodies + GRH antagonist

Nivolumab + BMS-986253 + degareliz

MAGIC-8

Hormone-Sensitive PC

Phase I, Phase II clinical trials

NCT03689699

PD-1

Pembrolizumab

PERSEUS1

CRPC

Phase II clinical trial

NCT03506997

anti- IgG2 subtype binding and neutralizing (RANKL)

denosumab

Open-Label Access Protocol of Denosumab for Subjects With Advanced Cancer

Bone Metastases in Men With Hormone-Refractory PC

Phase III clinical trial

NCT01419717

AR Antagonist + a dual DNA-PK/TOR kinase (DNAPK/TORK) inhibitor

Enzalutamide + CC-115

A Phase 1b Study of Enzalutamide Plus CC-115 in Men With CRPC

PC; CRPC

Phase I clinical trial

NCT02833883

anti-Trop-2 antibody (hRS7) conjugated to SN-38 payload

IMMU-132: ADC based on a humanized

IMMU-132 on Second Generation AR-Directed Therapy

CRPC

Phase 2 clinical trial

NCT03725761

LSD1 inhibitors

GSK2870552

Preclinical study

GSK-LSD1

Preclinical study

RN-1

Preclinical study

[21] [22]

SP-2509

Preclinical study

Cytochrome P450 17A1inhibitor/Combinatorial approaches

Radium-223 Dichloride causing double-strand breaks in DNA + Abiraterone Acetate

ERA 223

CRPC

Phase III clinical trial

NCT02043678

Abiraterone Acetate + Enzalutamide + Erdatifinib

Erdafitinib and Abiraterone Acetate or Enzalutamide in Treating Patients With Double Negative PC

Double negative PC

Phase II clinical trial

NCT03999515

Abiraterone acetate (CB7630) + Prednisone/prednisolone

Abiraterone Acetate in CRPC Previously Treated With Docetaxel-Based Chemotherapy

CRPC

Phase III clinical trial

NCT00638690

EZH2 inhibitors

GSK126

Preclinical study

GSK343

Preclinical study

[23]

GSK503

Preclinical study

Aurora-A

MLN8237

Aurora Kinase A Inhibitor MLN8237 in Patients With Metastatic Castrate Resistant and Neuroendocrine PC

NEPC

Phase II clinical trial

NCT01799278

BRN2 inhibitor

BRN2i

Small cell PC

Preclinical studies

[24]

eIF2α/eIF2S1 Ser51 Phosphorylation inhibitor

ISRIB

Aggressive PC progression

Preclinical studies

[25]

Double-strand breaks in DNA + cyclical, high-dose testosterone administration

radium 223- Bipolar Androgen Therapy (BAT)

BAT-RAD

CRPC

Phase 2 clinical trial

NCT04704505

XPO-1 inhibitor

selinexor

Preclinical studies

[26]

hypoxic regions of solid tumors

selective hypoxia-activated prodrug Evofosfamide (TH-302)

Preclinical studies

[27]

AR/FlnA complex

Rh-2025 u

Preclinical studies in PC and PC-TME

[28]

AR/Src complex

S1 peptide

Preclinical studies in PC

[29]