The evolution of financial incentives in the U.S. health care system

Darves-Bornoz, Annie; Resnick, Matthew J.

doi:10.1016/j.urolonc.2016.09.011

Cited by 12 publications

(7 citation statements)

References 10 publications

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“…As expression and function of AR-V7 (and other constitutively active AR variants) is a key mechanism underlying resistance to current PC treatments (10, 18, 21-24), it is imperative to develop novel AR inhibitors that target the N-terminal domain, which is present in both FL-AR and AR splice variants (reviewed in 51). Since AR-Vs may function either as homodimers or heterodimers with FL-AR (13, 22) and promote ligand-independent AR activity (13, 25, 26), therapeutic modalities must address both possible modes of AR-V action.…”

Section: Discussionmentioning

confidence: 99%

“…AR-Vs confer castration resistance in vitro and in vivo , and their presence in PC tumors and circulating tumor cells denotes poor prognosis (10, 18, 21, 22, 23). A recent study by Antonarakis et al 2017 (24), which was performed in 202 patients, underlines the clinical significance of AR-V7 in human PC samples by demonstrating a correlation between AR-V7 levels and therapeutic resistance to ADT.…”

Section: Introductionmentioning

confidence: 97%

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Targeting AR Variant–Coactivator Interactions to Exploit Prostate Cancer Vulnerabilities

Magani

Peacock

Rice

et al. 2017

Molecular Cancer Research

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Castration-resistant prostate cancer (CRPC) progresses rapidly and is incurable. Constitutively active androgen receptor splice variants (AR-Vs) represent a well-established mechanism of therapeutic resistance and disease progression. These variants lack the AR ligand-binding domain and, as such, are not inhibited by androgen deprivation therapy (ADT), which is the standard systemic approach for advanced PC. Signaling by AR-Vs, including the clinically relevant AR-V7, is augmented by Vav3, an established AR coactivator in CRPC. Using mutational and biochemical studies, we demonstrated that the Vav3 Diffuse B-cell lymphoma homology (DH) domain interacted with the N-terminal region of AR-V7 (and full length AR). Expression of the Vav3 DH domain disrupted Vav3 interaction with and enhancement of AR-V7 activity. The Vav3 DH domain also disrupted AR-V7 interaction with other AR coactivators: Src1 and Vav2, which are overexpressed in PC. This Vav3 domain was used in proof-of-concept studies to evaluate the effects of disrupting the interaction between AR-V7 and its coactivators on CRPC cells. This disruption decreased CRPC cell proliferation and anchorage-independent growth, caused increased apoptosis, decreased migration, and resulted in the acquisition of morphological changes associated with a less aggressive phenotype. While disrupting the interaction between FL-AR and its coactivators decreased N-C terminal interaction, disrupting the interaction of AR-V7 with its coactivators decreased AR-V7 nuclear levels. Implications This study demonstrates the potential therapeutic utility of inhibiting constitutively active AR-V signaling by disrupting coactivator binding. Such an approach is significant, as AR-Vs are emerging as important drivers of CRPC that are particularly recalcitrant to current therapies.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Targeting AR Variant–Coactivator Interactions to Exploit Prostate Cancer Vulnerabilities

Magani

Peacock

Rice

et al. 2017

Molecular Cancer Research

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“…In addition, the CONUT score has received focus as a predictor of survival in patients with several cancers. [6,7,9,10,18] In the present study, we evaluated the predictive value of the CONUT score and further compared the accuracy of this biomarker with PNI, NLR, and PLR in RCC patients. In the present study, each of these 4 indexes were associated with the OS and CSS in the univariate analysis.…”

Section: Discussionmentioning

confidence: 99%

Prognostic impact of the Controlling Nutritional Status score following curative nephrectomy for patients with renal cell carcinoma

Zheng

Bao²,

Wang

et al. 2018

Medicine

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“…Yes, obstacles will occur along the way, with more road-blocks than simple bumps. On the other hand, the economic [202,203] and social pressures (e.g., increasing use of electronic technology) [204,205], to increase patient empowerment [206,207,208]) are likely to be insurmountable.…”

Section: The Futurementioning

confidence: 99%

Characteristics of Future Models of Integrated Outpatient Care

et al. 2019

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Replacement of fee-for-service with capitation arrangements, forces physicians and institutions to minimize health care costs, while maintaining high-quality care. In this report we described how patients and their families (or caregivers) can work with members of the medical care team to achieve these twin goals of maintaining—and perhaps improving—high-quality care and minimizing costs. We described how increased self-management enables patients and their families/caregivers to provide electronic patient-reported outcomes (i.e., symptoms, events) (ePROs), as frequently as the patient or the medical care team consider appropriate. These capabilities also allow ongoing assessments of physiological measurements/phenomena (mHealth). Remote surveillance of these communications allows longer intervals between (fewer) patient visits to the medical-care team, when this is appropriate, or earlier interventions, when it is appropriate. Systems are now available that alert medical care providers to situations when interventions might be needed.

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The evolution of financial incentives in the U.S. health care system

Cited by 12 publications

References 10 publications

Targeting AR Variant–Coactivator Interactions to Exploit Prostate Cancer Vulnerabilities

Targeting AR Variant–Coactivator Interactions to Exploit Prostate Cancer Vulnerabilities

Prognostic impact of the Controlling Nutritional Status score following curative nephrectomy for patients with renal cell carcinoma

Characteristics of Future Models of Integrated Outpatient Care

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