PARP Inhibitors in the Neoadjuvant Setting; A Comprehensive Overview of the Rationale for their Use, Past and Ongoing...

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Poly (ADP-ribose) polymerases (PARPs) are crucial for DNA damage repair via poly-ADP-ribosylation.
• Homologous recombination repair deficiency (HRD) cancers exhibit increased reliance on PARP for DNA repair.
• PARP inhibitors (PARPis) exploit synthetic lethality for targeted cancer therapy in HRD tumors.

Purpose of the Study:

• To review the rationale for using PARP inhibitors (PARPis) in the neoadjuvant cancer treatment setting.
• To evaluate current early-phase and ongoing clinical trials investigating neoadjuvant PARPis.
• To assess the potential of PARPis in treating cancers with homologous recombination repair deficiency (HRD).

Main Methods:

• Literature review of studies on neoadjuvant PARPi treatment for HRD-related cancers.
• Analysis of clinical trial data, focusing on breast, ovarian, prostate, and pancreatic cancers.
• Evaluation of emerging research on combination therapies and expanded outcome measures.

Main Results:

• Neoadjuvant PARPi trials are predominantly in breast and ovarian cancers.
• Limited Phase II/III evidence exists for neoadjuvant PARPi efficacy in prostate and pancreatic cancers.
• Ongoing studies are exploring neoadjuvant PARPi for HRD-related cancers.

Conclusions:

• PARP inhibitors show promise in the neoadjuvant treatment of HRD cancers, particularly in ovarian and breast cancer.
• Further research is needed to establish efficacy in prostate and pancreatic cancers.
• Future directions include combination strategies with immune checkpoint inhibitors and incorporating quality-of-life metrics.