Atrial Fibrillation and Cancer Patients: Mechanisms and Management.

PURPOSE OF REVIEW: Cancer-related mortality has significantly declined over the past several decades as a result of improved screening, diagnostics, and therapeutics. Although cancer patients and survivors are living longer, there is increased risk of both short-term and long-term cardiovascular complications, including arrhythmia. In this review, we highlight the current evidence detailing the connections between atrial fibrillation and cancer, provide insight into the mechanisms driving this relationship, and share practical considerations for the management of atrial fibrillation in cancer patients and cancer survivors. RECENT FINDINGS: Atrial fibrillation is an increasingly recognized condition among cancer patients, with epidemiological data showing increased incidence and worse outcomes in patients with cancer. Studies also describe a bidirectional relationship between cancer and atrial fibrillation, attributable in part to shared risk factors but also potentially due to shared biology. Cancer treatment-associated arrhythmia is an active area of investigation, with ongoing research to identify the mechanisms and pathophysiology behind this phenomenon. Furthermore, management of atrial fibrillation in patients with cancer presents unique challenges, particularly in management of anti-coagulation. Cancer patients have increased risk of developing atrial fibrillation due to the shared risk factors and biology of the two conditions. Moreover, various cancer therapeutics are known to be arrhythmogenic; however, mechanisms remain unclear. Further research is needed to better understand the pathophysiology of atrial fibrillation in cancer patient in order to establish prevention and treatment strategies specific to this population.

p85α is a microRNA target and affects chemosensitivity in pancreatic cancer.

BACKGROUND: We previously identified a correlation between increased expression of the phosphoinositide 3-kinase (PI3K) regulatory subunit p85α and improved survival in human pancreatic ductal adenocarcinoma (PDAC). The purpose of this study was to investigate the impact of changes in p85α expression on response to chemotherapy and the regulation of p85α by microRNA-21 (miR-21). MATERIALS AND METHODS: PDAC tumor cells overexpressing p85α were generated by viral transduction, and the effect of p85α overexpression on sensitivity to gemcitabine was tested by MTT assay. Primary human PDAC tumors were stained for p85α and miR-21 via immunohistochemistry and in situ hybridization, respectively. Additionally, PDAC cells were treated with miR-21 mimic, and changes in p85α and phospho-AKT were assessed by Western blot. Finally, a luciferase reporter assay system was used to test direct regulation of p85α by miR-21. RESULTS: Higher p85α expression resulted in increased sensitivity to gemcitabine (P < 0.01), which correlated with decreased PI3K-AKT activation. Human tumors demonstrated an inverse correlation between miR-21 and p85α expression levels (r = -0.353, P < 0.001). In vitro, overexpression of miR-21 resulted in decreased levels of p85α and increased phosphorylation of AKT. Luciferase reporter assays confirmed the direct regulation of p85α by miR-21 (P < 0.01). CONCLUSIONS: Our results demonstrate that p85α expression is a determinant of chemosensitivity in PDAC. Additionally, we provide novel evidence that miR-21 can influence PI3K-AKT signaling via its direct regulation of p85α. These data provide insight into potential mechanisms for the known relationship between increased p85α expression and improved survival in PDAC.