The COVID-19 pandemic has driven an unprecedented level of global activity in drug discovery and clinical development for effective therapeutics targeting the coronavirus disease. There are currently 744 therapeutics being tested in 2879 clinical trials globally. Almost 90% of these clinical trials are focused on monotherapies. Combination therapies are the mainstay of antiviral therapeutics to increase the potency of the individual compounds and to combat the rapid evolution of resistance, although combination therapies have inherently complex clinical and regulatory development challenges. Increased understanding of the SARS-CoV-2 lifecycle and COVID-19 pathology provides a scientific rationale for evaluating the effectiveness of different combinations. In this paper, we provide an overview of the current clinical trial landscape for combination therapeutics targeting COVID-19 through weekly scanning of national and international clinical trial registries. Our analysis delves specifically into dual combination therapies in what can be defined as "pivotal clinical trials" (active, randomised, controlled and at least phase II), with a focus on new and repurposed therapeutic candidates that have shown positive signals and/or been granted authorisation for emergency use based on positive efficacy and safety data.
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http://dx.doi.org/10.1111/bcp.15089 | DOI Listing |
JCO Clin Cancer Inform
January 2025
SimBioSys Inc, Chicago, IL.
Purpose: Perfusion modeling presents significant opportunities for imaging biomarker development in breast cancer but has historically been held back by the need for data beyond the clinical standard of care (SoC) and uncertainty in the interpretability of results. We aimed to design a perfusion model applicable to breast cancer SoC dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) series with results stable to low temporal resolution imaging, comparable with published results using full-resolution DCE-MRI, and correlative with orthogonal imaging modalities indicative of biophysical markers.
Methods: Subsampled high-temporal-resolution DCE-MRI series were run through our perfusion model and resulting fits were compared for consistency.
Blood Res
January 2025
Hematology Laboratory, General Hospital of Mexico "Dr. Eduardo Liceaga", Mexico City, Mexico.
Purpose: Despite advances in the treatment of adult acute lymphoblastic leukemia (ALL), relapse remains the most significant challenge in improving prognosis. Measurable residual disease (MRD) assessment can predict bone marrow relapse based on MRD positivity. As access to innovative therapies remains limited because of the high cost, chemotherapy is the widely utilized treatment option.
View Article and Find Full Text PDFJ Gastrointest Cancer
January 2025
MM Medical College Sadopur, Haryana, India.
Purpose: Neoadjuvant chemotherapy followed by esophagectomy is the usual approach to manage esophageal squamous cell carcinoma (ESCC). The optimal interval to operate after completion of neoadjuvant chemoradiotherapy (NACRT) still remains controversial.
Methods: A prospective study was conducted to observe and compare postoperative complications and pathological outcomes in patients with squamous cell carcinoma of the esophagus who underwent NACRT followed by surgery within 8 weeks or after 8 weeks of NACRT completion.
Antimicrob Agents Chemother
January 2025
Merck & Co., Inc, Rahway, New Jersey, USA.
The development of new and improved antiretroviral therapies that allow for alternative dosing schedules is needed for people living with HIV-1. Islatravir is a deoxyadenosine analog in development for the treatment of HIV-1 that suppresses HIV-1 replication via multiple mechanisms of action, including reverse transcriptase translocation inhibition and delayed chain termination. Islatravir is differentiated from other HIV-1 antiretrovirals by its high potency, long , broad tissue distribution, and favorable drug resistance profile.
View Article and Find Full Text PDFJ Mater Chem B
January 2025
Department of Gastrointestinal Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
Hypoxia, a condition that enhances tumor invasiveness and metastasis, poses a significant challenge for diverse cancer therapies. There is a pressing demand for hypoxia-responsive nanoparticles with integrated photodynamic functions in order to address the aforementioned issues and overcome the reduced efficacy caused by tumor hypoxia. Here, we report a hypoxia-responsive supramolecular nanoparticle SN@IR806-CB consisting of a dendritic drug-drug conjugate (IR806-Azo-CB) and anionic water-soluble [2]biphenyl-extended-pillar[6]arene modified with eight ammonium salt ions (AWBpP6) the synergy of π-π stacking interaction, host-guest complexation, and hydrophobic interactions for synergistic photothermal therapy (PTT), photodynamic therapy (PDT), and chemotherapy (CT; , PTT-PDT-CT).
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