Table 1.

Subset of Mutations Found in mCRPC and the Percent Occurrence as Measured in Patient Tumor Tissue or from Blood Sequencing Cell Free DNA

Genomic Alteration by Pathway	Patient % (Tumor DNA)	Patient % (Cell Free DNA)	Relevance to Cell Cycle and Prostate Cancer	Combination with CDK4/6 Inhibitor
AR (amplification)	62.730	2232	Increase Cyclin D Reduction in p27 and p21 Inactivation of tumor suppressor Rb	ASI HDACi
P53* (loss of function)	47–53.331,92	3632	Loss of tumor suppressor effects Decrease p21 activity	TP53 modulators
RAS/RAF/MAPK (oncogene activation)	4.7–3231,92	1832	Inactivation of tumor suppressor Rb, inactivation of p53 CDK4/6i resistance	MEKi TP53 modulator
PTEN* (loss of function)	40.7–4331,92	NR	PI3K/AKT activation CDK4/6i resistance	AKTi HDACi
DNA Repair* (loss of function)	19–2431,92	1032	Susceptible to PARP inhibitors Induce HRR deficiency with CDK4/6i via down regulating MYC and FOXM1	PARPi
PI3K (amplification)	8–13.931,92	532	Growth in absence of AR signaling CDK4/6i resistance	PI3Ki AKTi HDACi
FGFR (amplification)	1092	NR	Increase cyclin D1 CDK4/6i resistance	FGFRi
SPOP (oncogene activation)	830	NR	Mutation increases PD-L1, decreases CD3+ TILs, increase tumor growth	Immunotherapy HDACi
Cell cycle (amplification)	4.730	NR	Potential susceptibility to CDK4/6i	FOXM1-FOX3 axis

Abbreviations: ASI, androgen signaling inhibitor; HDACi, HDAC inhibitor; NR, Not reported; TILs, tumor infiltrating lymphocytes; HRR, homologous recombinant repair; *tumor suppressor.