DNA damage is one of the hallmarks of cancer. However, cancer cells also rely on the DNA damage response (DDR) repair mechanisms to maintain a balance against overt DNA damage and subsequent cell death. These mechanisms include nucleotide excision repair (NER), base excision repair (BER), mismatch repair (MMR), homologous recombination (HR) and nonhomologous end-joining (NHEJ) pathways.
Many gynecological cancers have defects in DDR pathways. Three key kinases - ataxia telangiectasia mutated (ATM), ataxia telangiectasia and RAD3 related (ATR), and DNA-dependent protein kinase (DNA-PK) - and many other downstream pathways and genes have therefore been exploited as therapeutic targets for synthetic lethality. For example, PARP1 inhibition impairs the repair of single-strand DNA breaks (SSB), which can lead to the accumulation of double-strand breaks (DSB). In cells with HR deficiency or BRCA mutations, the DSB cannot be effectively repaired and cell death follows.
As the prognosis of patients with advanced/recurrent gynecological cancers remains poor, there is an urgent need to develop more efficient therapeutic agents. However, there is still a knowledge gap in the biology of these cancers. This Research Topic's aim is to tackle this deficiency in gynecologic malignancies, focusing on DDR, by providing an overview on the etiology of DNA damage and replication stress in gynecologic cancers, the interplay with other mechanisms, how this can be exploited as a therapeutic potential, their resistance mechanisms, and how these can be studied in different models.
We welcome Original Research articles, including preclinical and translational studies, and Clinical Trials; Review articles will also be considered. Topics of interest include, but are not limited to:
1. DDR pathways and cellular machinery in different female genital tract malignancies;
2. Interaction of DNA damage with other pathways such as cell cycle arrest, apoptosis and inflammation;
3. Combination therapies with chemotherapy, radiotherapy, immunotherapy and other targeted agents;
4. Biomarkers related to therapies targeting DDR;
5. Resistance mechanisms to therapies targeting DDR;
6. Different in vitro and in vivo model systems such as primary cultures, organoid cultures and genetically engineered mice studying DDR and related pathways.
Prospective Authors, please note – cell line studies must demonstrate the applicability of anticancer modalities on a minimum of two well-authenticated cancer cell lines.
Studies consisting solely of in silico investigation without experimental or in situ validation to support conclusions are not in scope for the Women's Cancer section.
DNA damage is one of the hallmarks of cancer. However, cancer cells also rely on the DNA damage response (DDR) repair mechanisms to maintain a balance against overt DNA damage and subsequent cell death. These mechanisms include nucleotide excision repair (NER), base excision repair (BER), mismatch repair (MMR), homologous recombination (HR) and nonhomologous end-joining (NHEJ) pathways.
Many gynecological cancers have defects in DDR pathways. Three key kinases - ataxia telangiectasia mutated (ATM), ataxia telangiectasia and RAD3 related (ATR), and DNA-dependent protein kinase (DNA-PK) - and many other downstream pathways and genes have therefore been exploited as therapeutic targets for synthetic lethality. For example, PARP1 inhibition impairs the repair of single-strand DNA breaks (SSB), which can lead to the accumulation of double-strand breaks (DSB). In cells with HR deficiency or BRCA mutations, the DSB cannot be effectively repaired and cell death follows.
As the prognosis of patients with advanced/recurrent gynecological cancers remains poor, there is an urgent need to develop more efficient therapeutic agents. However, there is still a knowledge gap in the biology of these cancers. This Research Topic's aim is to tackle this deficiency in gynecologic malignancies, focusing on DDR, by providing an overview on the etiology of DNA damage and replication stress in gynecologic cancers, the interplay with other mechanisms, how this can be exploited as a therapeutic potential, their resistance mechanisms, and how these can be studied in different models.
We welcome Original Research articles, including preclinical and translational studies, and Clinical Trials; Review articles will also be considered. Topics of interest include, but are not limited to:
1. DDR pathways and cellular machinery in different female genital tract malignancies;
2. Interaction of DNA damage with other pathways such as cell cycle arrest, apoptosis and inflammation;
3. Combination therapies with chemotherapy, radiotherapy, immunotherapy and other targeted agents;
4. Biomarkers related to therapies targeting DDR;
5. Resistance mechanisms to therapies targeting DDR;
6. Different in vitro and in vivo model systems such as primary cultures, organoid cultures and genetically engineered mice studying DDR and related pathways.
Prospective Authors, please note – cell line studies must demonstrate the applicability of anticancer modalities on a minimum of two well-authenticated cancer cell lines.
Studies consisting solely of in silico investigation without experimental or in situ validation to support conclusions are not in scope for the Women's Cancer section.
