Tumor Mutation Burden

[venecia1983]

Last genetic test has shwon TMB 10.86 and the orevious one (in March, 2023) showed the value of 8.68. Will increased TMB require the addition of PARP inhibitors to my current therapy consisting of Loupron and Abiraterone? Anyone has similar experience?

My history can be seen under bio. Just to add that I had 6 Pluvicto treatments with undetectable PSA since 12/22. The last Pluvicto was in April, 2023 and June PSA was undetectable. In Sept it shows 3.00 PSA and scan showed multiple lymph nodes that unfortunetaly cannot be radiated (1 is too close to duodenum).

Thank you for any thoughts

[Tall_Allen]

PARP inhibitors have no relation I know of with TMB - where did you hear that? Keytruda may work somewhat better, though.

[venecia1983 in reply to Tall_Allen]

Thanks Allen. It was my interpretation and it look s that I was wrong. Just spoke with a dr and he suggests Jevtana+Nubequa+Lupron. TMB is too low for any immune therapy.

[Medline]

Immune checkpoint inhibitors may be more effective than cabazitaxel in patients with TMB≥10 [jamanetwork.com/journals/ja...]. PARP inhibitors work by inhibiting DNA repair, which leads to DNA damage and increased TMB.

[lokibear0803 in reply to Medline]

Could you explain the increased TMB after DNA damage?

[PCaWarrior in reply to Medline]

Why is TMB increased via PARP inhibitors? DNA damage can increase TMB. But specifically how do unrepaired DNA DSBs, and subsequent immediate cell death, increase TMB?

I practice BAT and use PARP inhibitors at select times (I'm not BRCA). The theory was to induce DNA DSBs and then inhibit SSB and DSB repair. My TMB went from 8 to 6 to undetectable.