1,721,134 research outputs found
From dominance to decline: can we reverse the trend in small molecule and TKI cancer therapies?
No full text: Over the past two decades, precision oncology has seen unprecedented advances, particularly with the rise of small molecule drugs. These drugs have significantly benefitted patients with cancer harboring somatic genomic alterations, contributing to precision cancer medicine. Despite their early promise, there is a growing concern that major pharmaceutical companies are recently moving away from developing small molecules and tyrosine kinase inhibitors (TKIs) due to market saturation, primary and secondary resistance, and economic factors. The Inflation Reduction Act (IRA) further threatens innovation by reducing incentives for small molecule drug development. Additionally, patient access to comprehensive genomic testing remains a significant barrier. To reverse this trend, a multifaceted approach is urgently needed. Embracing cutting-edge technologies, fostering collaborations, and regulatory innovation are essential. Addressing systemic deficiencies, improving patient access, and ensuring ongoing investment in personalized medicine are crucial for realizing the full potential of small molecule oncology drugs and improving patient outcomes. Collaboration among stakeholders is imperative for advancing effective cancer treatments
The emerging role of PI3K inhibitors for solid tumour treatment and beyond
Full text linkPhosphoinositide 3-kinases (PI3Ks) play a central role in tumourigenesis with recurrent activating mutations of its p110 alpha subunit (PIK3CA) identified in several tumours. Although several PI3K inhibitors are approved for haematological malignancies, only alpelisib was approved in solid tumours and for the treatment of PIK3CA-related overgrowth spectrum (PROS) syndrome. Traditional PI3K inhibitors inhibit both wild-type and mutant PI3K with almost equal potency, thus limiting their efficacy due to on-target toxicity. Since the initiation of phase I clinical trials investigating next generation allosteric mutant and isoform selective PIK3CA inhibitors, there has been a surge in interest in PIK3CA targeting in solid tumours. Preclinical characterisation of these compounds showed that maximal mutant protein inhibition fails to elicit metabolic and glucose homoeostasis dysregulation, one of the dose limiting toxicities of both selective and pan PI3K inhibitors. While extreme selectivity can be hypothesised to grant activity and safety advantage to these novel agents, on the other hand reduced benefit can be speculated for patients harbouring multiple or rare PIK3CA mutations. This review summarises the current understanding of PI3K alterations and the state-of-the-art treatment strategies in PI3K driven solid tumours, while also exploring the potential intrinsic and acquired resistance mechanisms to these agents, and the emerging role of mutant selective PIK3CA inhibitors
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Challenges and barriers for the adoption of personalized medicine in Europe: the case of Oncotype DX Breast Recurrence Score® test
No full textPersonalized medicine, aiming to tailor treatments based on individual patient characteristics, holds immense potential in oncology. However, its widespread adoption in Europe faces numerous challenges, as illustrated by the case study of the Oncotype DX Breast Recurrence Score® assay, a genomic test for breast cancer. This manuscript delineates the multifaceted obstacles encountered during the introduction of the Oncotype DX®test (Oncotype DX Breast Recurrence Score test) in Europe from 2004 to 2018. In June 2018, the TAILORx results were published in the New England Journal of Medicine Sparano JA, Gray RJ, Makower DF, Pritchard KI, Albain KS, Hayes DF, et al. Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer. N Engl J Med 2018;379:111–21, Sparano JA, Gray RJ, Ravdin PM, Makower DF, Pritchard KI, Albain KS, et al. Clinical and genomic risk to guide the use of adjuvant therapy for breast cancer. N Engl J Med 2019;380:2395–405, and reported that among 6,711 women with hormone-receptor–positive, HER2-negative, node–negative breast cancer and a midrange recurrence score of 11–25 on the Oncotype DX assay, endocrine therapy was not inferior to chemoendocrine therapy, which provides evidence that adjuvant chemotherapy was not beneficial in these patients. Through a comprehensive analysis of clinical evidence, commercial presence, reimbursement mechanisms, guideline recommendations, regulatory pathways, and local experiences, this study sheds light on the intricate dynamics influencing the adoption of personalized medicine technologies. This article examines the various obstacles encountered during the introduction of the Oncotype DX Breast Cancer Assay in Europe from 2004 to 2018. By analyzing clinical evidence, commercial presence, reimbursement mechanisms, guideline recommendations, regulatory pathways, and local experiences, this study reveals the complex factors that influence the adoption of personalized medicine technologies. By highlighting these challenges, this article offers valuable insights into strategies to facilitate the integration of innovative diagnostic tools into clinical practice across Europe, ultimately leading to improved treatment decision-making for cancer patients
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