Author:
Virginie Baylot, Thi Khanh Le, David Taïeb, Palma Rocchi, Laurence Colleaux
Publication Date:
23 Apr 2024
Source:
Communications Biology
Description:
Rare diseases (RD) affect a small number of people compared to the general population and are mostly genetic in origin. The first clinical signs often appear at birth or in childhood, and patients endure high levels of pain and progressive loss of autonomy frequently associated with short life expectancy. Until recently, the low prevalence of RD and the gatekeeping delay in their diagnosis have long hampered research. The era of nucleic acid (NA)-based therapies has revolutionized the landscape of RD treatment and new hopes arise with the perspectives of disease-modifying drugs development as some NA-based therapies are now entering the clinical stage. Herein, we review NA-based drugs that were approved and are currently under investigation for the treatment of RD. We also discuss the recent structural improvements of NA-based therapeutics and delivery system, which overcome the main limitations in …
Author:
Thi Khanh Le, Quang Hieu Duong, Virginie Baylot, Christelle Fargette, Michael Baboudjian, Laurence Colleaux, David Taïeb, Palma Rocchi
Publication Date:
19 Oct 2023
Description:
Simple Summary Castration-resistant prostate cancer (CRPC) remains a significant medical challenge, even with recent advancements in diagnosis and treatment. To improve patient outcomes, it is important to understand the underlying mechanisms of resistance to treatments and develop new therapeutic approaches. This review provides a brief summary of the current knowledge on the mechanisms that contribute to CRPC progression, including both androgen receptor (AR)-dependent and AR-independent pathways. It also discusses approved and currently investigated treatment options to treat patients with CRPC, such as novel chemotherapies, radiation therapy, immunotherapy, PARP inhibitors, and potential combined therapeutic strategies. Abstract Prostate cancer (PC) is the second most common cancer in men worldwide. Despite recent advances in diagnosis and treatment, castration-resistant prostate cancer (CRPC) remains a significant medical challenge. Prostate cancer cells can develop mechanisms to resist androgen deprivation therapy, such as AR overexpression, AR mutations, alterations in AR coregulators, increased steroidogenic signaling pathways, outlaw pathways, and bypass pathways. Various treatment options for CRPC exist, including androgen deprivation therapy, chemotherapy, immunotherapy, localized or systemic therapeutic radiation, and PARP inhibitors. However, more research is needed to combat CRPC effectively. Further investigation into the underlying mechanisms of the disease and the development of new therapeutic strategies will be crucial in improving patient …
Author:
Sandra Udu-Ituma, José Adélaïde, Thi Khanh Le, Kenneth Omabe, Pascal Finetti, Clément Paris, Arnaud Guille, François Bertucci, Daniel Birnbaum, Palma Rocchi, Max Chaffanet
Publication Date:
11 Jul 2023
Description:
The luminal B molecular subtype of breast cancers (BC) accounts for more than a third of BCs and is associated with aggressive clinical behavior and poor prognosis. The use of endocrine therapy in BC treatment has significantly contributed to the decrease in the number of deaths in recent years. However, most BC patients with prolonged exposure to estrogen receptor (ER) selective modulators such as tamoxifen develop resistance and become non-responsive over time. Recent studies have implicated overexpression of the ZNF703 gene in BC resistance to endocrine drugs, thereby highlighting ZNF703 inhibition as an attractive modality in BC treatment, especially luminal B BCs. However, there is no known inhibitor of ZNF703 due to its nuclear association and non-enzymatic activity. Here, we have developed an antisense oligonucleotide (ASO) against ZNF703 mRNA and shown that it downregulates ZNF703 protein expression. ZNF703 inhibition decreased cell proliferation and induced apoptosis. Combined with cisplatin, the anti-cancer effects of ZNF703-ASO9 were improved. Moreover, our work shows that ASO technology may be used to increase the number of targetable cancer genes.
Author:
Meg Critcher, Lara A Gruijs da Silva, Dorothee Dormann, Zachary T Campbell, Thi Khanh Le, Palma Rocchi, Michèle Sorgenfrei
Publication Date:
01 Feb 2023
Source:
Trends in Biochemical Sciences
Description:
From the back of an envelope to the front of an article For us, the process of designing a summary figure or graphical abstract normally starts when the article is fully (or almost) written up and the main message that we want to convey is clear. We then start by sketching different rough versions on a piece of paper and alter it until we have a version that best illustrates our key points. During this brainstorming phase, we have in consideration:(i) the main key words/phrases that the reader should catch and make sure to minimize the use of text; and (ii) the target audience, in order to choose terms or graphical elements that the readers are likely familiar with; for example, a lay audience may require the use of analogies from everyday life instead of technical terms and jargon.Next, we move our idea to a digital platform. Our favorite online tool is BioRender because it allows us to create high-quality figures in a short time …
Author:
Thi Khanh Le, Chaïma Cherif, Kenneth Omabe, Clément Paris, François Lannes, Stéphane Audebert, Emilie Baudelet, Mourad Hamimed, Dominique Barbolosi, Pascal Finetti, Cyrille Bastide, Ladan Fazli, Martin Gleave, François Bertucci, David Taïeb, Palma Rocchi
Publication Date:
01 Feb 2023
Source:
Molecular Therapy
Description:
The heat shock protein 27 (Hsp27) has emerged as a principal factor of the castration-resistant prostate cancer (CRPC) progression. Also, an antisense oligonucleotide (ASO) against Hsp27 (OGX-427 or apatorsen) has been assessed in different clinical trials. Here, we illustrate that Hsp27 highly regulates the expression of the human DEAD-box protein 5 (DDX5), and we define DDX5 as a novel therapeutic target for CRPC treatment. DDX5 overexpression is strongly correlated with aggressive tumor features, notably with CRPC. DDX5 downregulation using a specific ASO-based inhibitor that acts on DDX5 mRNAs inhibits cell proliferation in preclinical models, and it particularly restores the treatment sensitivity of CRPC. Interestingly, through the identification and analysis of DDX5 protein interaction networks, we have identified some specific functions of DDX5 in CRPC that could contribute actively to tumor …
Author:
Asma Bourefis, Hajira Berredjem, Omar Djeffal, Thi Khanh Le, Sophie Giusiano, Palma Rocchi
Publication Date:
29 Sep 2022
Description:
Simple Summary Cancer biomarkers are biomolecules synthesized by the tumor cell and have a role in early detection of cancer and determining its stage and progression. HSP27 and Menin are biomolecules involved in tumorigenesis and cancer progression; they are overexpressed in many cancers and could be useful as biomarkers. However, the overexpression of HSP27 and Menin in the serum of prostate cancer (PCa) patients and the correlation they have with their tissue expression, as well as their correlation with the clinical data, have not been explored yet. In this study, we first investigated the correlations between HSP27 and Menin in PCa patients, and then we examined the signification of HSP27/Menin in the diagnosis and prognosis of PCa using ROC analysis. Our results suggest that HSP27/Menin are dependent biomarkers in aggressive PCa and are significantly associated with poor prognosis; they could be used in the diagnosis and clinical decision making of individual PCa patients. Abstract The screening of PCa is based on two tests, the total PSA test and the rectal examination. However, PSA is not specific for PCa stage confirmation, leading in false positive result and involving PCa over-diagnosis and over-treatment. HSP27 and Menin have been found to be overexpressed in a wide range of human cancers. Recent studies showed how HSP27 interacts with and stabilizes Menin to lead PCa progression and treatment resistance. The purpose of our study was to evaluate the correlation of HSP27 and Menin molecular expression, and their prognosis value in PCa with respect to …
Author:
M Baboudjian, M Gauthé, E Barret, Laurent Brureau, P Rocchi, G Créhange, Charles Dariane, G Fiard, G Fromont, J-B Beauval, R Mathieu, R Renard-Penna, G Roubaud, A Ruffion, P Sargos, M Rouprêt, G Ploussard
Publication Date:
01 Jun 2022
Source:
Progrès en Urologie
Description:
Introduction : L’objectif de cette revue narrative menée par le Comité Prostate de l’Association Française d’Urologie (CCAFU) était de rapporter les données les plus récentes concernant l’utilisation de la TEP/TDM dans la prise en charge des hommes atteints de cancer de la prostate résistant à la castration non métastatique (CPRCnm).Matériel et Méthodes : Cette revue est basée sur les données disponibles dans la littérature sur la TEP/TDM pour la stadification du CPRCnm. Une recherche PubMed et un examen narratif des données ont été réalisé en mars 2022. Seuls les articles en français ou en anglais ont été pris en compte.Résultats : Les directives actuelles recommandent la scintigraphie osseuse et la tomodensitométrie comme modalités d’imagerie standard pour la stadification et le suivi des patients atteints de CPRCnm. Près d’un tiers des patients asymptomatiques avec un CPRCnm présentent une …
Author:
M Baboudjian, M Gauthé, E Barret, Laurent Brureau, P Rocchi, G Créhange, Charles Dariane, G Fiard, G Fromont, J-B Beauval, R Mathieu, R Renard-Penna, G Roubaud, A Ruffion, P Sargos, M Rouprêt, G Ploussard
Publication Date:
01 Jun 2022
Source:
Progrès en Urologie
Description:
Introduction : L’objectif de cette revue narrative menée par le Comité Prostate de l’Association Française d’Urologie (CCAFU) était de rapporter les données les plus récentes concernant l’utilisation de la TEP/TDM dans la prise en charge des hommes atteints de cancer de la prostate résistant à la castration non métastatique (CPRCnm).Matériel et Méthodes : Cette revue est basée sur les données disponibles dans la littérature sur la TEP/TDM pour la stadification du CPRCnm. Une recherche PubMed et un examen narratif des données ont été réalisé en mars 2022. Seuls les articles en français ou en anglais ont été pris en compte.Résultats : Les directives actuelles recommandent la scintigraphie osseuse et la tomodensitométrie comme modalités d’imagerie standard pour la stadification et le suivi des patients atteints de CPRCnm. Près d’un tiers des patients asymptomatiques avec un CPRCnm présentent une …
Author:
Chaïma Cherif, Dang Tan Nguyen, Clément Paris, Thi Khanh Le, Thibaud Sefiane, Nadine Carbuccia, Pascal Finetti, Max Chaffanet, Abdessamad El kaoutari, Julien Vernerey, Ladan Fazli, Martin Gleave, Mohamed Manai, Philippe Barthélémy, Daniel Birnbaum, François Bertucci, David Taïeb, Palma Rocchi
Publication Date:
03 Jan 2022
Description:
Disease progression and therapeutic resistance of prostate cancer (PC) are linked to multiple molecular events that promote survival and plasticity. We previously showed that heat shock protein 27 (HSP27) acted as a driver of castration-resistant phenotype (CRPC) and developed an oligonucleotides antisense (ASO) against HSP27 with evidence of anti-cancer activity in men with CRPC. Here, we show that the tumor suppressor Menin (MEN1) is highly regulated by HSP27. Menin is overexpressed in high-grade PC and CRPC. High MEN1 mRNA expression is associated with decreased biochemical relapse-free and overall survival. Silencing Menin with ASO technology inhibits CRPC cell proliferation, tumor growth, and restores chemotherapeutic sensitivity. ChIP-seq analysis revealed differential DNA binding sites of Menin in various prostatic cells, suggesting a switch from tumor suppressor to oncogenic …
Author:
Dang Tan Nguyen, Thi Khanh Le, Clément Paris, Chaïma Cherif, Stéphane Audebert, Sandra Oluchi Udu-Ituma, Sébastien Benizri, Philippe Barthélémy, François Bertucci, David Taïeb, Palma Rocchi
Publication Date:
08 Jul 2021
Description:
The tumor suppressor menin has dual functions, acting either as a tumor suppressor or as an oncogene/oncoprotein, depending on the oncological context. Triple-negative breast cancer (TNBC) is characterized by the lack of expression of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (ERBB2/HER2) and is often a basal-like breast cancer. TNBC is associated with a dismal prognosis and an insufficient response to chemotherapies. Previously, menin was shown to play a proliferative role in ER-positive breast cancer; however, the functions of menin in TNBC remain unknown. Here, we have demonstrated that menin is expressed in various TNBC subtypes with the strongest expression in the TNBC Hs 578T cells. The depletion of menin by an antisense oligonucleotide (ASO) inhibits cell proliferation, enhances apoptosis in Hs 578T cells, highlighting the oncogenic functions of menin in this TNBC model. ASO-based menin silencing also delays the tumor progression of TNBC xenografts. Analysis of the menin interactome suggests that menin could drive TNBC tumorigenesis through the regulation of MLL/KMT2A-driven transcriptional activity, mRNA 3′-end processing and apoptosis. The study provides a rationale behind the use of ASO-based therapy, targeting menin in monotherapy or in combination with chemo or PARP inhibitors for menin-positive TNBC treatments.
