Lung cancer, a leading cause of cancer-related deaths globally, is characterized by significant genomic instability, which is a hallmark of various cancers. Despite advancements in understanding the molecular mechanisms underlying lung cancer and the development of targeted therapies, treatment options remain limited, particularly for advanced stages of the disease. Chemotherapeutic agents, especially platinum-based drugs like cisplatin, exploit this genomic instability by inducing DNA damage in rapidly dividing cancer cells. However, the emergence of chemotherapy-resistant tumors presents a significant challenge in treatment efficacy. The DNA damage repair (DDR) pathways play a critical role in maintaining genomic integrity and their dysregulation can lead to increased mutation rates and tumor progression. This research topic aims to explore the intricate relationship between DDR mechanisms and thoracic cancers, focusing on how these pathways can be targeted to improve therapeutic outcomes.

The primary goal of this research topic is to address the challenges posed by DNA damage repair mechanisms in thoracic cancers, particularly non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Despite initial responses to DNA-damaging agents, resistance often develops, undermining treatment effectiveness. To combat this issue, it is essential to investigate novel therapeutic strategies that target specific DDR pathways. This includes exploring the potential of inhibitors that disrupt key proteins involved in DDR. Furthermore, understanding the mechanisms of resistance that arise during treatment will be crucial for developing more effective combination therapies that integrate DDR inhibitors with existing treatments like immunotherapy. By identifying novel biomarkers associated with DDR deficiencies, we can enhance patient stratification and tailor treatments to improve clinical outcomes.

This Research Topic invites contributions that delve into various themes related to DNA damage repair in thoracic cancers. Specific areas of interest include:

• Mechanisms of DNA Damage Repair: Detailed analyses of homologous recombination (HR), non-homologous end joining (NHEJ), base excision repair (BER), and other pathways.
• Therapeutic Strategies: Investigations into novel inhibitors targeting DDR proteins and their combination with existing therapies.
• Biomarkers: Identification and validation of biomarkers predictive of response to DDR-targeted therapies.
• Resistance Mechanisms: Exploration of molecular mechanisms underlying resistance to DDR inhibitors.
• Tumor Heterogeneity: Studies addressing inter- and intra-tumoral heterogeneity and its impact on treatment outcomes.

We welcome a range of manuscript types, including original research articles, reviews, case studies, and commentaries that contribute to a deeper understanding of the role of DNA damage repair in thoracic cancers and its implications for therapy.

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Role of DNA Damage Repair in Thoracic Cancers

Topic Coordinator