A community effort in SARS-CoV-2 drug discovery.

peer reviewedThe COVID-19 pandemic continues to pose a substantial threat to human lives and is likely to do so for years to come. Despite the availability of vaccines, searching for efficient small-molecule drugs that are widely available, including in low- and middle-income countries, is an ongoing challenge. In this work, we report the results of an open science community effort, the "Billion molecules against Covid-19 challenge", to identify small-molecule inhibitors against SARS-CoV-2 or relevant human receptors. Participating teams used a wide variety of computational methods to screen a minimum of 1 billion virtual molecules against 6 protein targets. Overall, 31 teams participated, and they suggested a total of 639,024 molecules, which were subsequently ranked to find 'consensus compounds'. The organizing team coordinated with various contract research organizations (CROs) and collaborating institutions to synthesize and test 878 compounds for biological activity against proteases (Nsp5, Nsp3, TMPRSS2), nucleocapsid N, RdRP (only the Nsp12 domain), and (alpha) spike protein S. Overall, 27 compounds with weak inhibition/binding were experimentally identified by binding-, cleavage-, and/or viral suppression assays and are presented here. Open science approaches such as the one presented here contribute to the knowledge base of future drug discovery efforts in finding better SARS-CoV-2 treatments.R-AGR-3826 - COVID19-14715687-CovScreen (01/06/2020 - 31/01/2021) - GLAAB Enric

Tumeurs phyllodes et sarcomes primitifs mammaires (à propos d'une expérience multicentrique)

LILLE2-BU Santé-Recherche (593502101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Brain Metastasis Treatment: The Place of Tyrosine Kinase Inhibitors and How to Facilitate Their Diffusion across the Blood–Brain Barrier

International audienceThe incidence of brain metastases has been increasing constantly for the last 20 years, because of better control of metastases outside the brain, and the failure of most drugs to cross the blood-brain barrier at relevant pharmacological concentrations. Recent advances in the molecular biology of cancer have led to the identification of numerous molecular alterations, some of them targetable with the development of specific targeted therapies, including tyrosine kinase inhibitors. In this narrative review, we set out to describe the state-of-the-art in the use of tyrosine kinase inhibitors for the treatment of melanoma, lung cancer, and breast cancer brain metastases. We also report preclinical and clinical pharmacological data on brain exposure to tyrosine kinase inhibitors after oral administration and describe the most recent advances liable to facilitate their penetration of the blood-brain barrier at relevant concentrations and limit their physiological efflux

Reactive resistance to anti-angiogenic drugs

International audienc

Transgénèse et xénogreffe (deux stratégies expérimentales pour les thérapies innovantes en cancérologie)

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

Evaluation de la faisabilité d'une prise en charge adjuvante par trastuzumab du cancer du sein localisé chez le sujet âgé (>= 65 ans)

PARIS-BIUP (751062107) / SudocSudocFranceF

A Boom in Nanotechnologies for a High Level of Precision Medicine

The number of publications on nanomedicine in oncology has been exponential over the last ten years, going from 640 publications in 2012 to 2487 publications in 2022, reflecting the growing interest and potential of these new technologies [...

The Pharmacology of Xenobiotics after Intracerebro Spinal Fluid Administration: Implications for the Treatment of Brain Tumors

International audienceThe incidence of brain metastasis has been increasing for 10 years, with poor prognosis, unlike the improvement in survival for extracranial tumor localizations. Since recent advances in molecular biology and the development of specific molecular targets, knowledge of the brain distribution of drugs has become a pharmaceutical challenge. Most anticancer drugs fail to cross the blood–brain barrier. In order to get around this problem and penetrate the brain parenchyma, the use of intrathecal administration has been developed, but the mechanisms governing drug distribution from the cerebrospinal fluid to the brain parenchyma are poorly understood. Thus, in this review we discuss the pharmacokinetics of drugs after intrathecal administration, their penetration of the brain parenchyma and the different systems causing their efflux from the brain to the blood

How to Make Anticancer Drugs Cross the Blood–Brain Barrier to Treat Brain Metastases

International audienceThe incidence of brain metastases has increased in the last 10 years. However, the survival of patients with brain metastases remains poor and challenging in daily practice in medical oncology. One of the mechanisms suggested for the persistence of a high incidence of brain metastases is the failure to cross the blood–brain barrier of most chemotherapeutic agents, including the more recent targeted therapies. Therefore, new pharmacological approaches are needed to optimize the efficacy of anticancer drug protocols. In this article, we present recent findings in molecular data on brain metastases. We then discuss published data from pharmacological studies on the crossing of the blood–brain barrier by anticancer agents. We go on to discuss future developments to facilitate drug penetration across the blood–brain barrier for the treatment of brain metastases among cancer patients, using physical methods or physiological transporters