The latest medical research on Oncology
The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about oncology gathered by our medical AI research bot.
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The cancer microbiome.Nature Reviews Cancer
Collectively known as the microbiota, the commensal bacteria and other microorganisms that colonize the epithelial surfaces of our body have been s...
Author Correction: Molecular subtypes of small cell lung cancer: a synthesis of human and mouse model data.Nature Reviews Cancer
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Multiple drug transporters contribute to the placental transfer of emtricitabine.Antimicrobial Agents and Chemotherapy
Emtricitabine (FTC) is a first-line antiviral drug recommended for treatment of acquired immune deficiency syndrome during pregnancy. We hypothesiz...
In Vitro Activity of Levonadifloxacin (WCK 771) against Chlamydia pneumoniae.Antimicrobial Agents and Chemotherapy
Levonadifloxacin (WCK 771) is a novel, broad spectrum agent belonging to benzoquinolizine sub-class of fluoroquinolones.….
Evaluation of a library of FDA-approved drugs for their ability to potentiate antibiotics against multidrug resistant Gram-negative pathogens.Antimicrobial Agents and Chemotherapy
The Prestwick library was screened for antibacterial activity or 'antibiotic-resistance breaking' (ARB) potential against four species of Gram-nega...
To randomize, or not to randomize, that is the question: using data from prior clinical trials to guide future designs.Neuro-Oncology
Understanding the value of randomization is critical in designing clinical trials. Here, we introduce a simple and interpretable quantitative method to compare randomized designs versus single arm designs using indication-specific parameters derived from the literature. We demonstrate the approach through application to phase II trials in newly diagnosed glioblastoma (ndGBM).
We abstracted data from prior ndGBM trials and derived relevant parameters to compare phase II RCT and single arm designs within a quantitative framework. Parameters included in our model were (i) the variability of the primary endpoint distributions across studies, (ii) potential for incorrectly specifying the single arm trial's benchmark, and (iii) the hypothesized effect size. Strengths and weaknesses of RCT and single arm designs were quantified by various metrics, including power and false positive errors rates.
We applied our method to show that RCTs should be preferred to single arm trials for evaluating overall survival in ndGBM patients based on parameters estimated from prior trials. More generally, for a given effect size, the utility of randomization compared to single arm designs is highly dependent on (i) inter-study variability of the outcome distributions and (ii) on potential errors in selecting standard of care efficacy estimates for single arm studies.
A quantitative framework using historical data is useful in understanding the utility of randomization in designing prospective trials. For typical phase II ndGBM trials using OS as the primary endpoint, randomization should be preferred over single arm designs.
DNA methylation profiling to predict recurrence risk in meningioma: development and validation of a nomogram to optimize clinical management.Neuro-Oncology
Variability in standard-of-care classifications precludes accurate predictions of early tumor recurrence for individual patients with meningioma, limiting the appropriate selection of patients who would benefit from adjuvant radiotherapy to delay recurrence. We aimed to develop an individualized prediction model of early recurrence risk combining clinical and molecular factors in meningioma.
DNA methylation profiles of clinically annotated tumor samples across multiple institutions were used to develop a methylome model of 5-year recurrence-free survival (RFS). Subsequently, a 5-year meningioma recurrence score was generated using a nomogram that integrated the methylome model with established prognostic clinical factors. Performance of both models was evaluated and compared with standard-of-care models using multiple independent cohorts.
The methylome-based predictor of 5-year RFS performed favorably compared with a grade-based predictor when tested using the 3 validation cohorts (ΔAUC = 0.10, 95% CI: 0.03-0.018) and was independently associated with RFS after adjusting for histopathologic grade, extent of resection, and burden of copy number alterations (hazard ratio 3.6, 95% CI: 1.8-7.2, P < 0.001). A nomogram combining the methylome predictor with clinical factors demonstrated greater discrimination than a nomogram using clinical factors alone in 2 independent validation cohorts (ΔAUC = 0.25, 95% CI: 0.22-0.27) and resulted in 2 groups with distinct recurrence patterns (hazard ratio 7.7, 95% CI: 5.3-11.1, P < 0.001) with clinical implications.
The models developed and validated in this study provide important prognostic information not captured by previously established clinical and molecular factors which could be used to individualize decisions regarding postoperative therapeutic interventions, in particular whether to treat patients with adjuvant radiotherapy versus observation alone.
Targeting the PI3K/Akt/mTOR-pathway with the pan-Akt inhibitor GDC-0068 in PIK3CA-mutant breast cancer brain metastases.Neuro-Oncology
Activating mutations in the PI3K/AKT/mTOR-pathway occur in 43-70% of breast cancer brain metastasis patients. To date, the treatment of these patients presents an ongoing challenge, mainly because of the lack of targeted agents that are able to sufficiently penetrate the blood-brain barrier. GDC-0068 is a pan-Akt-inhibitor that has shown to be effective in various preclinical tumor models as well as in clinical trials. The purpose of this study was to analyze the efficacy of GDC-0068 in a breast cancer brain metastases model.
In in vitro studies, antitumor activity of GDC-0068 was assessed in PIK3CA-mutant and PIK3CA-wildtype breast cancer cell lines using cell viability and apoptosis assays, cell cycle analysis and Western blots. In vivo, the efficacy of GDC-0068 was analyzed in a PIK3CA-mutant breast cancer brain metastasis orthotopic xenograft mouse model and evaluated by repeated bioluminescent imaging and immunohistochemistry.
GDC-0068 decreased cell viability, induced apoptosis and inhibited phosphorylation of PRAS40 and p70 S6 kinase in a dose-dependent manner in PIK3CA-mutant breast cancer brain metastatic cell lines compared to PIK3CA-wildtype cell lines. In vivo, treatment with GDC-0068 notably inhibited the growth of PIK3CA-mutant tumors and resulted in a significant survival benefit compared to sham whereas no effect was detected in a PIK3CA-wildtype model.
This study suggests that the Akt-inhibitor GDC-0068 may be an encouraging targeted treatment strategy for breast cancer brain metastasis patients with activating mutations in the PI3K pathway. These data provide a rationale to further evaluate the efficacy of GDC-0068 in patients with brain metastases.
Barriers to Accrual and Enrollment in Brain Tumor Trials.Neuro-Oncology
Many factors contribute to the poor survival of malignant brain tumor patients, some of which are not easily remedied. However, one contributor to ...
Going to extremes: determinants of extraordinary response and survival in patients with cancer.Nature Reviews Cancer
Research into factors affecting treatment response or survival in patients with cancer frequently involves cohorts that span the most common range ...
Tertiary lymphoid structures in the era of cancer immunotherapy.Nature Reviews Cancer
Tertiary lymphoid structures (TLSs) are ectopic lymphoid organs that develop in non-lymphoid tissues at sites of chronic inflammation including tum...
The current state of randomized clinical trial evidence for prostate brachytherapy.Urol Oncol
Interstitial brachytherapy is one of several curative therapeutic options for the treatment of localized prostate cancer. In this review, we summar...