Repositioning PARP inhibitors in the treatment of thoracic malignancies

The evaluation of the homologous recombination repair (HRR) status is emerging as a predictive tumor agnostic biomarker for poly (ADP-ribose) polymerase (PARP) inhibition across different tumor types and testing for HRRsignature is currently a developing area with promising therapeutic implications. Treatment with PARP inhibitors (PARPi) either as single agent or in combination with chemotherapy have shown so far limited activity in patients with thoracic malignancies. A deeper understanding of the biological background underlying HRRdeficient tumors, along with the recent advent of new effective targeted and immunotherapeutic agents, prompted the design of a new generation of clinical trials investigating novel PARPi-combinations in patients with lung cancer as well as malignant pleural mesothelioma. In this review we briefly summarize the biological basis of the DNA damage response pathway inhibition and provide an updated and detailed overview of clinical trials testing different PARPi-combinations strategies in patients with thoracic malignancies.

Automated summary

The evaluation of the HRR status is becoming an important predictive biomarker for PARP inhibition in various tumor types, particularly in thoracic malignancies. Clinical trials are currently being conducted to explore the efficacy of novel PARPi combinations in patients with lung cancer and malignant pleural mesothelioma, taking advantage of the deeper understanding of HRR-deficient tumors and the development of new targeted and immunotherapeutic agents.