PARP Expression in mCRPC Cells
The question appears to conflate PARP protein expression with homologous recombination repair (HRR) gene mutations—PARP itself is ubiquitously expressed in nearly all cells, but approximately 23-30% of mCRPC patients harbor mutations in HRR genes that make them sensitive to PARP inhibitor therapy. 1, 2
Understanding PARP vs HRR Mutations
PARP (Poly ADP-ribose polymerase) is a DNA repair enzyme that is expressed in essentially all human cells, including prostate cancer cells. The clinically relevant question is not about PARP expression, but rather about the prevalence of HRR gene mutations that create synthetic lethality when PARP is inhibited. 1
Prevalence of HRR Mutations in mCRPC
Approximately 23-30% of patients with mCRPC harbor deleterious mutations in homologous recombination repair genes, making them candidates for PARP inhibitor therapy 1, 2, 3
Among these HRR mutations, roughly one-third involve BRCA1 or BRCA2 genes, which show the strongest response to PARP inhibitors 4
The 14 HRR genes relevant for PARP inhibitor therapy include: BRCA1, BRCA2, ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, RAD51B, RAD51C, RAD51D, and RAD54L 5
Specific Gene Mutation Frequencies
ATM mutations occur in approximately 1.6-2.1% of mCRPC cases, with this prevalence remaining stable across different population groups 5
BRCA2 mutations show the most striking association with mCRPC, though specific prevalence data varies by study 5
CHEK2 mutations are found in 2.1-13.3% of Japanese patients with mCRPC, though this may vary by ethnicity 6
Clinical Testing Implications
Both germline and somatic tumor testing should be performed using next-generation sequencing technologies to identify HRR mutations before initiating PARP inhibitor therapy 7
Circulating tumor DNA (ctDNA) testing from plasma samples can identify somatic alterations and is particularly useful when tissue biopsy is not feasible or to capture tumor heterogeneity 3
The preferred method for selecting patients for rucaparib treatment is somatic analysis using ctDNA samples, while any commercially available analytically and clinically validated assays can identify patients for olaparib treatment 5
Critical Distinction
The question likely seeks information about HRR mutation prevalence rather than PARP protein expression itself, as PARP is universally expressed but only becomes a therapeutic target in the context of HRR deficiency through the principle of synthetic lethality. 1, 2