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<p>Poly (ADP-ribose) polymerase inhibitors (PARPi) have emerged as an important single-agent targeted therapeutic option for a subpopulation of breast cancer patients. While PARPi combinations have shown synergy in the pre-clinical setting, concomitant regimens have shown limited clinical benefit. Optimizing treatment schedules is therefore needed to improve outcomes. Sequential dosing of PARPi with cytotoxic, targeted, or immune therapies can enhance efficacy by sustaining DNA damage, suppressing DNA repair, and modulating the immune response. This approach also decreases toxicity by exploiting differences in replication stress between normal and cancer cells. Here, we discuss the rationale for improved efficacy and enhanced tolerability with sequential PARPi approaches, supported by pre-clinical and clinical evidence.</p>

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Sequencing PARP inhibitors in breast cancer: lessons learned and emerging insights

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月15日

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  • Kenan Aloss,
  • Mallory I. Frederick,
  • Saima Hassan

摘要

Poly (ADP-ribose) polymerase inhibitors (PARPi) have emerged as an important single-agent targeted therapeutic option for a subpopulation of breast cancer patients. While PARPi combinations have shown synergy in the pre-clinical setting, concomitant regimens have shown limited clinical benefit. Optimizing treatment schedules is therefore needed to improve outcomes. Sequential dosing of PARPi with cytotoxic, targeted, or immune therapies can enhance efficacy by sustaining DNA damage, suppressing DNA repair, and modulating the immune response. This approach also decreases toxicity by exploiting differences in replication stress between normal and cancer cells. Here, we discuss the rationale for improved efficacy and enhanced tolerability with sequential PARPi approaches, supported by pre-clinical and clinical evidence.