Search results for "Drug Development"

MicroRNAs, the immune system and rheumatic disease.

2008

MicroRNAs (miRNAs) have been implicated in the pathogenesis of rheumatic disease and are, therefore, a potential target for drug development. This Review describes the well-established roles of miRNAs in hematopoiesis and the immune response, the molecular action of miRNAs in the simultaneous post-transcriptional regulation of multiple targets, and the evidence for roles of specific miRNAs in rheumatic disease. MicroRNAs (miRNAs) are short noncoding RNA molecules that modulate the expression of multiple target genes at the post-transcriptional level and are implicated in a wide array of cellular and developmental processes. In hematopoietic cells, miRNA levels are dynamically regulated duri…

The discovery of novel antitrypanosomal 4-phenyl-6-(pyridin-3-yl)pyrimidines

2021

Human African trypanosomiasis, or sleeping sickness, is a neglected tropical disease caused by Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense which seriously affects human health in Africa. Current therapies present limitations in their application, parasite resistance, or require further clinical investigation for wider use. Our work herein describes the design and syntheses of novel antitrypanosomal 4-phenyl-6-(pyridin-3-yl)pyrimidines, with compound 13, the 4-(2-methoxyphenyl)-6-(pyridine-3-yl)pyrimidin-2-amine demonstrating an IC50 value of 0.38 μM and a promising off-target ADME-Tox profile in vitro. In silico molecular target investigations showed rhodesain to be a pu…

A Long-Term Extension Study of Bevacizumab in Patients With Solid Tumors

2021

Abstract Background Bevacizumab has been studied in numerous clinical trials in multiple types of cancer; however, patients may receive bevacizumab over an extended period of time. This study assessed the long‐term safety and tolerability of bevacizumab among patients with solid tumors. Materials and Methods Patients enrolled in a Roche/Genentech‐sponsored trial who had derived benefit from bevacizumab therapy as monotherapy or in combination with anticancer drugs were eligible for continuation of bevacizumab in this long‐term extension (LTE) study. The primary endpoints were the incidence of adverse events (AEs) of Common Terminology Criteria for AEs (CTCAE) grade ≥3 related to bevacizumab…

Proliferation-, estrogen-, and T-cell-related metagenes to predict outcome after adjuvant/neoadjuvant chemotherapy for operable breast cancer in the …

2013

1014 Background: Predicting recurrence in operable breast cancer (BC) despite optimal chemotherapy would be relevant to new drug development and tailored treatments. Methods: A large series (n=3,154) of public Affymetrix gene-expression profiles (GEP) was used to define prognostic/predictive metagenes in different BC subtypes. In ER+/HER2- a proliferation and an ER-related metagene were combined to predict low, intermediate and high risk of recurrence. In TN and in HER2+ a T cell metagene was used to predict low, intermediate and high risk (higher expression associated with lower risk). The metagenes were validated in patients enrolled in the phase III ECTO trial (Gianni L. JCO 2009) and t…

In the literature: April 2018

2018

The most important aim of precision medicine is the selection of the best treatment for each individual patient. To achieve this objective, the analysis of the molecular changes that can occur due to tumour heterogeneity or after anticancer treatment is fundamental. A dynamical study of the disease could lead to the identification of specific targets, which need to be inhibited at time of tumour progression. By using high-throughput sequencing, it is possible to identify a very limited number of somatic mutations that can be exploited for cancer treatment and drug development. However, the ability to predict response to targeted agents needs to be further improved. To do this, parallel stud…

Abstract CT201: The Mutanome Engineered RNA Immuno-Therapy (MERIT) project

2015

Abstract The Mutanome Engineered RNA Immuno-Therapy (MERIT) consortium will clinically and industrially validate a pioneering RNA-based immunotherapy concept that targets individual tumor antigens and tumor-specific mutations in triple negative breast cancer (TNBC) patients. This biomarker-guided, personalized therapy is a collaborative effort of five partners from academia and industry and is funded by the European Commission's FP7 and led by BioNTech AG. TNBC is an aggressive, molecularly heterogeneous cancer that accounts for 20% of all breast cancer patients. The 5-year survival rate is less than 80%. The molecular heterogeneity across TNBCs results in a lack of common targetable molecu…

Investigator-initiated trials of targeted oncology agents: why independent research is at risk?

2010

Background: Drug development traditionally has relied upon the complementary contributions of clinicians and scientists at academic institutions and at pharmaceutical companies. Greater regulatory burdens, increased bureaucratic requirements, restricted reimbursement, and spiralling research and development costs are exerting pressure on the drug development pipeline. The result is a de-emphasis of exploratory research, particularly independent academic research, despite its proven value in identifying new drug targets and developing innovative cancer therapies. Design: An expert panel assembled by the Biotherapy Development Association-a nonprofit international forum for academic and indus…

The regulatory landscape for actively personalized cancer immunotherapies

2013

Precision Medicine to Treat Advanced Gastroesophageal Adenocarcinoma: A Work in Progress

2020

Gastroesophageal adenocarcinoma (GEA) represents a heterogeneous disease and, when diagnosed as locally advanced or metastatic, it is characterized by poor prognosis. During the last few years, several molecular classifications have been proposed to try to personalize treatment for those patients diagnosed with advanced disease. Nevertheless, despite the great effort, precision medicine is still far from being a reality. The improvement in the molecular analysis due to the application of high throughput technologies based on DNA and RNA sequencing has opened a novel scenario leading to the personalization of treatment. The possibility to target epidermal growth factor receptor (HER)2, Claud…

Six years of progress in the oral biopharmaceutics area - A summary from the IMI OrBiTo project.

2020

OrBiTo was a precompetitive collaboration focused on the development of the next generation of Oral Biopharmaceutics Tools. The consortium included world leading scientists from nine universities, one regulatory agency, one non-profit research organisation, three small/medium sized specialist technology companies together with thirteen pharmaceutical companies. The goal of the OrBiTo project was to deliver a framework for rational application of predictive biopharmaceutics tools for oral drug delivery. This goal was achieved through novel prospective investigations to define new methodologies or refinement of existing tools. Extensive validation has been performed of novel and existing biop…