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The Akt pathway in oncology therapy and beyond (Review).

ABSTRACT: Protein kinase B (Akt), similar to many other protein kinases, is at the crossroads of cell death and survival, playing a pivotal role in multiple interconnected cell signaling mechanisms implicated in cell metabolism, growth and division, apoptosis suppression and angiogenesis. Akt protein kinase displays important metabolic effects, among which are glucose uptake in muscle and fat cells or the suppression of neuronal cell death. Disruptions in the Akt?regulated pathways are associated with cancer, diabetes, cardiovascular and neurological diseases. The regulation of the Akt signaling pathway renders Akt a valuable therapeutic target. The discovery process of Akt inhibitors using various strategies has led to the identification of inhibitors with great selectivity, low side?effects and toxicity. The usefulness of Akt emerges beyond cancer therapy and extends to other major diseases, such as diabetes, heart diseases, or neurodegeneration. This review presents key features of Akt structure and functions, and presents the progress of Akt inhibitors in regards to drug development, and their preclinical and clinical activity in regards to therapeutic efficacy and safety for patients.

SUBMITTER: Nitulescu GM

PROVIDER: S-EPMC6203150 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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The Akt pathway in oncology therapy and beyond (Review).

Nitulescu George Mihai GM Van De Venter Maryna M Nitulescu Georgiana G Ungurianu Anca A Juzenas Petras P Peng Qian Q Olaru Octavian Tudorel OT Grădinaru Daniela D Tsatsakis Aristides A Tsoukalas Dimitris D Spandidos Demetrios A DA Margina Denisa D

International journal of oncology 20181016 6

Protein kinase B (Akt), similar to many other protein kinases, is at the crossroads of cell death and survival, playing a pivotal role in multiple interconnected cell signaling mechanisms implicated in cell metabolism, growth and division, apoptosis suppression and angiogenesis. Akt protein kinase displays important metabolic effects, among which are glucose uptake in muscle and fat cells or the suppression of neuronal cell death. Disruptions in the Akt‑regulated pathways are associated with can ...[more]

PMID: 30334567

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Project description:BACKGROUND:Telehealth services are rapidly embraced in uro-oncology due to the current coronavirus disease 2019 (COVID-19) pandemic. OBJECTIVE:To determine patients' perspective on adoption of telehealth as a response to the pandemic and its sustainability in the future. DESIGN, SETTING, AND PARTICIPANTS:Following a COVID-19 outbreak, 101 patients with advanced genitourinary cancers are currently managed "virtually" for therapy administration at our tertiary care unit. They were surveyed about the current situation, and current and long-term employment of telehealth. INTERVENTION:Rapid implementation of virtual patient management. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:Patients' perception of anxiety of COVID-19 and cancer, perspective on telehealth measures as a reaction to the current COVID-19 pandemic, and long-term acceptance were used as outcomes. Wilcoxon matched-pair signed rank test, chi-square test, and Mann-Whitney U test were performed. RESULTS AND LIMITATIONS:Of 101 patients, 92 answered the questionnaire, with 71 (77.2%) responding virtually by e-mail or phone call. Anxiety of cancer (6/10, interquartile range [IQR] 3-8) superseded that of COVID-19 (four/10, IQR 2-5.25, p<0.001), and patients oppose temporary treatment interruption. Of the patients, 66.0% perceive their susceptibility to COVID-19 as equal to or lower than the general population and 52.2% believe that COVID-19 will not affect their therapy. In future, patients (62.6%) prefer to maintain in-person appointments as opposed to complete remote care, but accept remote care during the pandemic (eight/10, IQR 5-9). Beyond the crisis, maintaining telehealth has low preference rates (four/10, IQR 2-7), with high acceptance for external laboratory controls (60.9%) and online visit management (48.9%), but lower acceptance for remote treatment planning including staging discussions (44.6%) and for referral to secondary care oncologists (17.4%). CONCLUSIONS:Despite the pandemic, cancer remains the key concern and patients are not willing to compromise on their treatment. Rapid implementation of telehealth is tolerated well during the need of social distancing, with a clear "red line" concerning changes in existing patient-physician relationships. Balancing future implementation of telehealth while considering patients' demand for personal relationships will ensure human dignity in uro-oncology. PATIENT SUMMARY:We queried patients with genitourinary cancers treated in an almost virtual setting following a local coronavirus outbreak. Acceptance of telehealth during the current situation is high; however, long-term implementation of the adapted services is less favored. We deduce that patient-physician relationship is crucial for cancer patients and needs to be balanced against measures for social distancing to forge the future management.

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The Akt pathway in oncology therapy and beyond (Review).

Publications

The Akt pathway in oncology therapy and beyond (Review).

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