Table 1.

Select genomic alterations and their future clinical implications

Pathway process	Targets	Drug development	Potential prognostic or predictive biomarkers
AR signalling	AR NCOR1/2 FOXA1 ZBTB16 SPOP	N-terminal domain AR inhibitors; Dual AR/GR inhibitors	AR-V7 spice variants; AR amplification
Cell cycle	P53 MYC CDKN2A RB1 AURKA	DNA-binding domain AR inhibitors; CDK4/6 inhibitors; AURKA inhibitors	RB1 status; AR lo/independence; AURKA amplification
DNA repair	BRCA ATM RAD51 MSH2/6 SPOP DNAPK	PARP inhibitors, PD- L1 inhibitors	DNA repair defects
ETS Fusion	ERG ETV1	HDAC inhibitors, PARP inhibitors	ETS gene fusion status
MAPK pathway	BRAF RAF1 HRAS	BRAF inhibitors; MEK inhibitors	Mutations or gene fusions
Wnt pathway	CTNNB1 APC ZNRF3 RNF43 RSPO2	Porcupine inhibitors	Mutations or gene fusions
PI3K pathway	PTEN PIK3CA PI3KCB AKT1	pan-PI3K and dual PI3K– mTOR inhibitors; PI3KCB inhibitors	Mutations or copy number alterations

AKT, v⁻akt murine thymoma viral oncogene homologue; APC, adenomatous polyposis coli; AR, androgen receptor; BRAF, B-Raf proto-oncogene, serine/threonine kinase; BRCA, breast cancer; CTNNB1, catenin β 1; ERG, v⁻ets avian erythroblastosis virus E26 oncogene homologue; ETS variant 1; FOXA1, forkhead box A1; GR, glucocorticoid receptor; HDAC, histone deacetylases; HRAS, Harvey rat sarcoma viral oncogene homologue; MSX, msh homeobox; MYC, MYC proto-oncogene protein; NCOR, nuclear receptor co-repressor; PARP, poly(ADP-ribose) polymerase; PD-L1, programmed cell death 1 ligand 1; PIK3C, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit; PTEN, phosphatase and tensin homologue; RAD51, RAD51 recombinase; RAF1, Raf-1 proto-oncogene, serine/threonine kinase; RB1, retinoblastoma 1; RNF43, ring finger protein 43; RSPO2, R-spondin 2; SPOP, speckle type BTB/POZ protein; ZBTB16, zinc finger and BTB domain containing 16; ZNRF3, zinc and ring finger 3.