PARP Inhibitors for Breast Cancer Treatment: A Review.

Abstract

Importance:

Poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors have revolutionized the treatment of patients with germline BRCA1/2-associated breast cancer, representing the first targeted therapy capable of improving outcomes in patients with hereditary tumors. However, resistance to PARP inhibitors occurs in almost all patients.

Observations:

This narrative review summarizes the biological rationale behind the use of PARP inhibitors in breast cancer, as well as the available evidence, recent progress, and potential future applications of these agents. Recent studies have shown that the benefit of PARP inhibitors extends beyond patients with germline BRCA1/2-associated metastatic breast cancer to patients with somatic BRCA1/2 variants and to those with germline PALB2 alterations. Moreover, these agents proved to be effective both in the metastatic and adjuvant settings. However, patients with metastatic breast cancer usually do not achieve the long-term benefit from PARP inhibitors observed in other tumor types. Mechanisms of resistance have been identified, but how to effectively target them is largely unknown. Ongoing research is investigating both novel therapeutics and new combination strategies to overcome resistance. PARP1-selective inhibitors, by sparing the hematological toxic effects induced by the PARP2 blockade, are promising agents to be combined with chemotherapy, antibody-drug conjugates, and other targeted therapies.

Conclusions and Relevance:

Although the efficacy of PARP inhibitors is well established, many questions persist. Future research should focus on identifying predictive biomarkers and therapeutic strategies to overcome resistance. Integrating well-designed translational efforts into all clinical studies is thereby crucial to laying the groundwork for future insights from ongoing research.

• Authors: Stefania Morganti, Antonio Marra, Carmine De Angelis, Angela Toss, Luca Licata, Federica Giugliano, Beatrice Taurelli Salimbeni, Pier Paolo Maria Berton Giachetti, Angela Esposito, Antonio Giordano, Giampaolo Bianchini, Judy E Garber, Giuseppe Curigliano, Filipa Lynce, Carmen Criscitiello
• Journal: JAMA oncology (JAMA Oncol) Vol. 10 Issue 5 Pg. 658-670 (May 01 2024) ISSN: 2374-2445 [Electronic] United States
• PMID: 38512229 (Publication Type: Journal Article, Review)

Chemical References

• BRCA1 protein, human
• BRCA2 protein, human

Topics

• Humans
• Poly(ADP-ribose) Polymerase Inhibitors (therapeutic use)
• Breast Neoplasms (drug therapy, genetics, pathology)
• Female
• Drug Resistance, Neoplasm
• BRCA1 Protein (genetics)
• BRCA2 Protein (genetics)
• Antineoplastic Agents (therapeutic use, adverse effects)
• Poly (ADP-Ribose) Polymerase-1 (antagonists & inhibitors)
• Treatment Outcome