About this Research Topic
Genomic instability and mutagenesis are fundamental enablers of tumorigenesis and cancer genome evolution. However, in order to thrive, cancer cells are forced to maintain a balance between genome plasticity and excessive gene disruption, making them susceptible to genotoxic perturbation by chemotherapeutic agents. DNA repair and replication stress responses enable cancer cells to maintain optimal genome plasticity and also allow them to survive treatment with chemotherapeutic agents. Furthermore, cancers arising from genetic defects in DNA repair and replication exhibit heightened dependencies on alternate DNA repair pathways. Thus, therapeutic strategies involving targeting DNA repair pathways, which exploit the increased reliance on DNA repair in cancer, offer tremendous potential in improving patient outcomes.
In recent years, significant progress has been made in uncovering novel modalities by which DNA repair dependencies can be effectively targeted in cancer. Notable examples include PARP inhibitors which selectively target BRCA-deficient cancers and the recent identification of WRN as a prime target for microsatellite unstable cancers. Moreover, functional genomics approaches have not only identified additional synthetic lethal targets in DNA repair deficient cancers, but also uncovered mechanisms by which rewired DNA repair can cause therapeutic resistance. Additionally, mechanisms underlying DNA sequence alteration have been found to act as predictors of tumorigenesis, as well as directly influence therapy response. Thus, gaining a deeper understanding of how DNA repair and the replication stress response operate in cancer has important implications in developing novel and effective therapies as well as predicting cancer etiology.
The present Research Topic aims at building a focus on the latest developments in DNA damage, repair and replication in the context of cancer and will include articles pertinent - but not solely limited to the following areas:
• DNA repair and replication associated dependencies in cancer.
• Mechanisms underlying the DNA damage and replication stress response.
• Mechanisms of chemo- and radio- and targeted therapy resistance.
• Novel targets and therapeutic strategies involving DNA damage and repair.
• Mechanisms of mutagenesis and cancer genome evolution.
• Biomarkers underlying DDR pathway dependency.
In recent years, significant progress has been made in uncovering novel modalities by which DNA repair dependencies can be effectively targeted in cancer. Notable examples include PARP inhibitors which selectively target BRCA-deficient cancers and the recent identification of WRN as a prime target for microsatellite unstable cancers. Moreover, functional genomics approaches have not only identified additional synthetic lethal targets in DNA repair deficient cancers, but also uncovered mechanisms by which rewired DNA repair can cause therapeutic resistance. Additionally, mechanisms underlying DNA sequence alteration have been found to act as predictors of tumorigenesis, as well as directly influence therapy response. Thus, gaining a deeper understanding of how DNA repair and the replication stress response operate in cancer has important implications in developing novel and effective therapies as well as predicting cancer etiology.
The present Research Topic aims at building a focus on the latest developments in DNA damage, repair and replication in the context of cancer and will include articles pertinent - but not solely limited to the following areas:
• DNA repair and replication associated dependencies in cancer.
• Mechanisms underlying the DNA damage and replication stress response.
• Mechanisms of chemo- and radio- and targeted therapy resistance.
• Novel targets and therapeutic strategies involving DNA damage and repair.
• Mechanisms of mutagenesis and cancer genome evolution.
• Biomarkers underlying DDR pathway dependency.
Keywords: DNA Damage; DNA Replication; Replication Stress; Genome Stability; Mutagenesis; Chemotherapy; Chemoresistance; Radioresistance; Targeted Therapy
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
