HRD testing influence eligibility for PARP inhibitors?

HRD testing influence eligibility for PARP inhibitors?

• A. HRD testing has no effect on eligibility.
• B. They exclude BRCA-mutant tumors.
• C. HRD testing or germline BRCA mutations support use; some approvals require BRCA mutation, others include broader HRD-positive tumors.
• D. Only germline BRCA testing matters

Answer: (C)

PARP inhibitors exploit the vulnerability created when homologous recombination repair is defective. If BRCA1/2 function is lost, whether due to a germline mutation or a somatic tumor alteration, cells rely more on PARP-mediated repair, so blocking PARP leads to accumulation of DNA damage and tumor cell death. HRD testing looks for this repair deficiency in the tumor, including cases without a BRCA mutation, identifying tumors that may still respond to PARP inhibitors. Clinically, drug approvals reflect this biology: some require a BRCA mutation to qualify, while others extend eligibility to tumors that are HRD-positive regardless of BRCA status. Therefore, HRD testing or germline BRCA mutations can support use, but the exact eligibility depends on the specific approval.

PARP inhibitors exploit the vulnerability created when homologous recombination repair is defective. If BRCA1/2 function is lost, whether due to a germline mutation or a somatic tumor alteration, cells rely more on PARP-mediated repair, so blocking PARP leads to accumulation of DNA damage and tumor cell death. HRD testing looks for this repair deficiency in the tumor, including cases without a BRCA mutation, identifying tumors that may still respond to PARP inhibitors. Clinically, drug approvals reflect this biology: some require a BRCA mutation to qualify, while others extend eligibility to tumors that are HRD-positive regardless of BRCA status. Therefore, HRD testing or germline BRCA mutations can support use, but the exact eligibility depends on the specific approval.