About this Research Topic
Ovarian cancer represents the leading cause of gynecological cancer-related mortality worldwide, which could be substantially attributed to its delayed diagnosis. Indeed, most patients typically present with advanced [International Federation of Gynecology and Obstetrics (FIGO) stage III-IV] disease, for which optimal debulking surgery and (neo)-adjuvant platinum-based chemotherapy remain the gold standard.
Recent advances in tumor biology have undoubtedly resulted in a tremendous shift in ovarian cancer management. In particular, the poly (ADP-ribose) polymerase (PARP) pathway inhibition, using novel small-molecule modulators of PARP enzymes, exploits “synthetic lethality” in homologous recombination deficient (HRD) tumors and constitutes a prominent example of targeted therapy successfully translated to clinical setting. Numerous pivotal trials led to FDA approval of PARP inhibitors, either as monotherapy or in combination with the antiangiogenic drug bevacizumab, as frontline maintenance treatment. Despite the promising initial responses, emergence of resistance is rather inevitable leading to incurable disease recurrence.
Several mechanisms of acquired resistance have been described in both preclinical and clinical studies, including HR pathway restoration either though BRCA1/2 function restoration or by rewiring of DNA damage response genetic networks, drug efflux upregulation, stalled replication forks stabilization, and epigenetic modifications. Considering not only that the aforementioned biological processes remain elusive, but also the intensive ongoing research to overcome the challenge of PARPi resistance, we welcome submissions of original studies, reviews, systematic reviews, and meta-analyses, and perspective articles that cover, but are not limited to:
- Cross-resistance between PARPi and platinum chemotherapy
- Current and potential combinational therapeutic strategies to overcome PARPi resistance
o Antiangiogenic agents
o Immunotherapy
o Targeting DNA Damage Response (ATR-, WEE1- POLθ- inhibitors, etc.)
o Combining DNA damage response (ATR-, WEE1- POLθ- inhibitors, etc.) with other agents
o Radiation therapy
- Therapy-related myeloid neoplasms
- Resistance mechanisms to PARP inhibition
o primary resistance to PARPi (location of mutation in BRCA1/2 genes)
o Secondary resistance to PARPi through HR restoration (Reversion mutations in BRCA1/2 genes)
o Other mechanisms of secondary resistance to PARPi (SFN11, PARG, etc.)
- Immune landscape of BRCA mutated tumors
Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic
Recent advances in tumor biology have undoubtedly resulted in a tremendous shift in ovarian cancer management. In particular, the poly (ADP-ribose) polymerase (PARP) pathway inhibition, using novel small-molecule modulators of PARP enzymes, exploits “synthetic lethality” in homologous recombination deficient (HRD) tumors and constitutes a prominent example of targeted therapy successfully translated to clinical setting. Numerous pivotal trials led to FDA approval of PARP inhibitors, either as monotherapy or in combination with the antiangiogenic drug bevacizumab, as frontline maintenance treatment. Despite the promising initial responses, emergence of resistance is rather inevitable leading to incurable disease recurrence.
Several mechanisms of acquired resistance have been described in both preclinical and clinical studies, including HR pathway restoration either though BRCA1/2 function restoration or by rewiring of DNA damage response genetic networks, drug efflux upregulation, stalled replication forks stabilization, and epigenetic modifications. Considering not only that the aforementioned biological processes remain elusive, but also the intensive ongoing research to overcome the challenge of PARPi resistance, we welcome submissions of original studies, reviews, systematic reviews, and meta-analyses, and perspective articles that cover, but are not limited to:
- Cross-resistance between PARPi and platinum chemotherapy
- Current and potential combinational therapeutic strategies to overcome PARPi resistance
o Antiangiogenic agents
o Immunotherapy
o Targeting DNA Damage Response (ATR-, WEE1- POLθ- inhibitors, etc.)
o Combining DNA damage response (ATR-, WEE1- POLθ- inhibitors, etc.) with other agents
o Radiation therapy
- Therapy-related myeloid neoplasms
- Resistance mechanisms to PARP inhibition
o primary resistance to PARPi (location of mutation in BRCA1/2 genes)
o Secondary resistance to PARPi through HR restoration (Reversion mutations in BRCA1/2 genes)
o Other mechanisms of secondary resistance to PARPi (SFN11, PARG, etc.)
- Immune landscape of BRCA mutated tumors
Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic
Keywords: PARP inhibitors, Resistance mechanisms, DNA Damage Response, Combinational treatment, Ovarian cancer, Therapy-related myeloid neoplasm, immunotherapy, Radiation 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.
