New Approaches in Early-Stage NSCL Management: Potential Use of PARP Inhibitors and Immunotherapy Combination

Abstract

Lung cancer is the second most common cancer in the world, being the first cause of cancer-related mortality. Surgery remains the only potentially curative treatment for Non-Small Cell Lung Cancer (NSCLC), but the recurrence risk remains high (30–55%) and Overall Survival (OS) is still lower than desirable (63% at 5 years), even with adjuvant treatment. Neoadjuvant treatment can be helpful and new therapies and pharmacologic associations are being studied. Immune Checkpoint Inhibitors (ICI) and PARP inhibitors (PARPi) are two pharmacological classes already in use to treat several cancers. Some pre-clinical studies have shown that its association can be synergic and this is being studied in different settings. Here, we review the PARPi and ICI strategies in cancer management and the information will be used to develop a clinical trial to evaluate the potential of PARPi association with ICI in early-stage neoadjuvant setting NSCLC.

Biological mechanisms of resistance to immune checkpoint inhibitors and overcoming this resistance: Challenges in medical oncology

“…As a result of damage to the micronuclei, DNA is released into the cytoplasm, which activates the innate immune system. An increase in TMB, increased neoantigen expression, activation of effector T cells, stimulation of dendritic cell maturation, and upregulation of PD-L1 were observed (Fernandes et al, 2023).…”