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Targeting Epigenetic Aberrations in Pancreatic Cancer, a New Path to Improve Patient Outcomes?

ABSTRACT: Pancreatic cancer has one of the highest mortality rates among all types of cancers. The disease is highly aggressive and typically diagnosed in late stage making it difficult to treat. Currently, the vast majority of therapeutic regimens have only modest curative effects, and most of them are in the surgical/neo-adjuvant setting. There is a great need for new and more effective treatment strategies in common clinical practice. Previously, pathogenesis of pancreatic cancer was attributed solely to genetic mutations; however, recent advancements in the field have demonstrated that aberrant activation of epigenetic pathways contributes significantly to the pathogenesis of the disease. The identification of these aberrant activated epigenetic pathways has revealed enticing targets for the use of epigenetic inhibitors to mitigate the phenotypic changes driven by these cascades. These pathways have been found to be responsible for overactivation of growth signaling pathways and silencing of tumor suppressors and other cell cycle checkpoints. Furthermore, new miRNA signatures have been uncovered in pancreatic ductal adenocarcinoma (PDAC) patients, further widening the window for therapeutic opportunity. There has been success in preclinical settings using both epigenetic inhibitors as well as miRNAs to slow disease progression and eliminate diseased tissues. In addition to their utility as anti-proliferative agents, the pharmacological inhibitors that target epigenetic regulators (referred to here as readers, writers, and erasers for their ability to recognize, deposit, and remove post-translational modifications) have the potential to reconfigure the epigenetic landscape of diseased cells and disrupt the cancerous phenotype. The potential to “reprogram” cancer cells to revert them to a healthy state presents great promise and merits further investigation.

SUBMITTER: Paradise BD

PROVIDER: S-EPMC5977101 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Targeting Epigenetic Aberrations in Pancreatic Cancer, a New Path to Improve Patient Outcomes?

Paradise Brooke D BD Barham Whitney W Fernandez-Zapico Martín E ME

Cancers 20180428 5

Pancreatic cancer has one of the highest mortality rates among all types of cancers. The disease is highly aggressive and typically diagnosed in late stage making it difficult to treat. Currently, the vast majority of therapeutic regimens have only modest curative effects, and most of them are in the surgical/neo-adjuvant setting. There is a great need for new and more effective treatment strategies in common clinical practice. Previously, pathogenesis of pancreatic cancer was attributed solely ...[more]

PMID: 29710783

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Project description:BackgroundThe Pancreatic Cancer Action Network (PanCAN) Patient Registry is an online, pancreatic cancer-specific, global registry enabling patients to self-report sociodemographics, disease/management characteristics, and patient-reported outcomes (PROs). We sought to describe the creation, user experience, and research potential of the PanCAN Registry.MethodsWe obtained data to describe (1) the creation of the Registry (questionnaire development, marketing efforts, and regulatory considerations); (2) the user experience (user characteristics and interactions with the registry following inception); and (3) the research potential of the registry (comparing PROs and treatment patterns by age [±65 years] and treatment site [community or academic] for users with de novo metastatic disease).ResultsThe Registry was conceived as part of PanCAN's strategic plan for a personalized therapy initiative. PanCAN staff and disease expert consultants developed questionnaires hosted on an electronic PRO platform. Users had the option to include their data in research efforts, and the Registry platform received institutional review board approval. From 7/2015 to 12/2020, 2187 patients visited the registry and 1697 (77.6%) completed at least one survey (median age = 64 years [range: 24-90], 47.9% women, 88.7% White, 34.0% metastatic disease). Among patients with metastatic disease (N = 567), 46.0% were ≥65 years old and 67.5% received treatment at community sites. Patients ≥65 years reported feeling less hopeful about the treatment plan (12.4% vs. 24.3%, p = 0.003), and patients treated at community sites reported more frequent treatment breaks of >2 weeks (58.2% vs. 28.1%, p < 0.001).ConclusionsOur findings demonstrate the feasibility, usability, and research potential of an online PRO registry for patients with cancer. This description of the PanCAN Registry should inform future registry-building efforts to facilitate standardized PRO reporting and provide a valuable research database.Clinical trial registration numberNot applicable.

Dataset Information

Targeting Epigenetic Aberrations in Pancreatic Cancer, a New Path to Improve Patient Outcomes?

Publications

Targeting Epigenetic Aberrations in Pancreatic Cancer, a New Path to Improve Patient Outcomes?

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