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Lessons, Challenges and Future Therapeutic Opportunities for PI3K Inhibition in CLL.

ABSTRACT: Chronic lymphocytic leukemia (CLL) shows constitutive phosphatidylinositol 3-kinase (PI3K) activation resulting from aberrant regulation of the B-cell receptor (BCR) signaling. PI3K inhibitors have been evaluated in CLL therapy, bringing a new treatment opportunity for patients with this disease. Despite the proven therapeutic efficacy, the use of approved PI3K inhibitors is limited by severe immune-mediated toxicities and given the availability of other more tolerable agents. This article reviews the relevance of PI3K signaling and pharmacologic inhibition in CLL. Data on efficacy and toxicity of PI3K inhibitors are also presented, as well as strategies for overcoming barriers for their clinical use in CLL treatment.

SUBMITTER: Guarente V

PROVIDER: S-EPMC7999552 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Lessons, Challenges and Future Therapeutic Opportunities for PI3K Inhibition in CLL.

Guarente Valerio V Sportoletti Paolo P

Cancers 20210313 6

Chronic lymphocytic leukemia (CLL) shows constitutive phosphatidylinositol 3-kinase (PI3K) activation resulting from aberrant regulation of the B-cell receptor (BCR) signaling. PI3K inhibitors have been evaluated in CLL therapy, bringing a new treatment opportunity for patients with this disease. Despite the proven therapeutic efficacy, the use of approved PI3K inhibitors is limited by severe immune-mediated toxicities and given the availability of other more tolerable agents. This article revie ...[more]

PMID: 33805745

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Project description:BackgroundIn Aotearoa/New Zealand, the first nation-wide coronavirus disease 2019 (COVID-19) lockdown occurred from March 23, 2020 to May 13, 2020, requiring most people to stay at home. Health services had to suddenly change how they delivered healthcare and some services were limited or postponed. This study investigated access to healthcare during this lockdown period, whether patients delayed seeking healthcare and reasons for these delays, focusing on the accessibility of primary care services.MethodsAdults (aged 18 years or older) who had contact with primary care services were invited through social media and email lists to participate in an online survey (n = 1010) and 38 people were recruited for in-depth interviews. We thematically analysed qualitative data from the survey and interviews, reported alongside relevant descriptive survey results.ResultsMore than half (55%) of survey respondents delayed seeking healthcare during lockdown. Factors at a national or health system-level that could influence delay were changing public service messages, an excessive focus on COVID-19 and urgent issues, and poor service integration. Influential factors at a primary care-level were communication and outreach, use of technology, gatekeeping, staff manner and the safety of the clinical practice environment. Factors that influenced patients' individual decisions to seek healthcare were the ability to self-manage and self-triage, consciousness of perceived pressure on health services and fear of infection.ConclusionIn future pandemic lockdowns or crises, appropriate access to primary care services can be improved by unambiguous national messages and better integration of services. Primary care practices should adopt rapid proactive outreach to patients, fostering a calm but safe clinical practice environment. More support for patients to self-manage and self-triage appropriately could benefit over-burdened health systems during lockdowns and as part of business as usual in less extraordinary times.

Dataset Information

Lessons, Challenges and Future Therapeutic Opportunities for PI3K Inhibition in CLL.

Publications

Lessons, Challenges and Future Therapeutic Opportunities for PI3K Inhibition in CLL.

Similar Datasets

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