Oncologists' Perspectives on Cancer Survivorship: What Role Should Primary Care Play?

Background: Despite calls for an enhanced role for primary care for individuals with a history of cancer, primary medical care's role in adult survivorship care continues to be marginal.Methods: We conducted in-depth interviews with 8 medical oncologists with interest in cancer survivorship from 7 National Cancer Institute designated comprehensive cancer centers to understand perspectives on the role of primary care in cancer survivorship.Results: Two salient overarching thematic patterns emerged. (1) Oncologist's perspectives diverge on if, how, and when primary care clinicians should be involved in survivorship, ranging from involvement of primary care throughout treatment to a standardized hand-off years post-therapy. (2) Oncologist's lack understanding about primary care's expertise and subsequent value in survivorship care.Conclusion: As oncology continues to be overwhelmed by rising numbers of aging cancer survivors with multi-morbidities, NCI-designated cancer centers should take a leadership role in integrating primary care engaged cancer survivorship.

Genetic or pharmacologic Nrf2 activation increases proteinuria in chronic kidney disease in mice.

The nuclear factor erythroid 2-related factor 2 (Nrf2) pathway upregulates key cellular defenses. Clinical trials are utilizing pharmacologic Nrf2 inducers such as bardoxolone methyl to treat chronic kidney disease, but Nrf2 activation has been linked to a paradoxical increase in proteinuria. To understand this effect, we examined genetically engineered mice with elevated Nrf2 signaling due to reduced expression of the Nrf2 inhibitor, Kelch-like ECH-associated protein 1 (Keap1). These Keap1FA/FA mice lacked baseline proteinuria but exhibited increased proteinuria in experimental models evoked by adriamycin, angiotensin II, or protein overload. After injury, Keap1FA/FA mice had increased glomerulosclerosis, nephrin disruption and shedding, podocyte injury, foot process effacement, and interstitial fibrosis. Keap1FA/FA mice also had higher daytime blood pressures and lower heart rates measured by radiotelemetry. Conversely, Nrf2 knockout mice were protected from proteinuria. We also examined the pharmacologic Nrf2 inducer CDDO-Im. Compared to angiotensin II alone, the combination of angiotensin II and CDDO-Im significantly increased proteinuria, a phenomenon not observed in Nrf2 knockout mice. This effect was not accompanied by additional increases in blood pressure. Finally, Nrf2 was found to be upregulated in the glomeruli of patients with focal segmental glomerulosclerosis, diabetic nephropathy, fibrillary glomerulonephritis, and membranous nephropathy. Thus, our studies demonstrate that Nrf2 induction in mice may exacerbate proteinuria in chronic kidney disease.