2Cleveland Clinic Center for Therapeutics Discovery (C3TD), Cleveland Clinic Research, Cleveland, Ohio, USA.
3College of Pharmacy, Korea University, Sejong, Korea.
Category: biotech/medical – Page 75
Biomarker-matched drug combos shrink treatment-resistant melanoma in preclinical models
A new study led by researchers at The University of Texas MD Anderson Cancer Center has identified a way to tailor drug combinations based on specific tumor biology to improve outcomes for treatment-resistant advanced melanoma.
In preclinical models from patients with treatment-resistant tumors, combining standard BRAF and MEK inhibitors with a drug to block proteins in the BCL2 family—which drive tumor growth—induced tumor regression in a molecularly defined subset of resistant tumors, suggesting a path toward biomarker-guided therapy.
The study, published in Nature Communications, was led by Vashisht Gopal Yennu Nanda, Ph.D., associate professor of Melanoma Medical Oncology and Translational Molecular Pathology, in collaboration with senior author Michael A. Davies, M.D., Ph.D., chair of Melanoma Medical Oncology.
Current Status and Perspectives of Dual-Targeting Chimeric Antigen Receptor T-Cell Therapy for the Treatment of Hematological Malignancies
Single-targeted chimeric antigen receptor (CAR) T cells tremendously improve outcomes for patients with relapsed/refractory hematological malignancies and are considered a breakthrough therapy. However, over half of treated patients experience relapse or refractory disease, with antigen escape being one of the main contributing mechanisms. Dual-targeting CAR T-cell therapy is being developed to minimize the risk of relapse or refractory disease. Preclinical and clinical data on five categories of dual-targeting CAR T-cell therapies and approximately fifty studies were summarized to offer insights and support the development of dual-targeting CAR T-cell therapy for hematological malignancies. The clinical efficacy (durability and survival) is validated and the safety profiles of dual-targeting CAR T-cell therapy are acceptable, although there is still room for improvement in the bispecific CAR structure. It is one of the best approaches to optimize the bispecific CAR structure by boosting T-cell transduction efficiency and leveraging evidence from preclinical activity and clinical efficacy.
Pathogenesis Induced by Influenza Virus Infection: Role of the Early Events of the Infection and the Innate Immune Response
Infections by influenza A virus (IAV) are a significant cause of global mortality. The pathogenesis of the infection is usually studied in terms of direct viral-induced damage or the overreactive immune response that continues after the virus is cleared. However, factors such as the initial infectious dose, the early response after infection in different cell types, and the presence of autoantibodies for relevant antiviral cytokines like type I IFNs seem to influence the course of the infection and lead to fatal outcomes. In this article, we address the current knowledge about the early events during influenza virus infection, which are important for their participation in influenza-derived pathogenesis.
Cognitive flexibility problems may arise months before memory impairment in Alzheimer’s
When most people think about Alzheimer’s disease, memory loss is usually the first thing that comes to mind. Forgetting a loved one’s name, missing appointments or repeatedly misplacing everyday items are often considered early warning signs. But what if the disease begins affecting the brain long before memory problems become noticeable? New research from scientists at Texas A&M Health suggests that another change in brain function may appear even earlier: difficulty adapting when circumstances change.
In a recent study published in Nature Communications, researchers found that animal models with Alzheimer’s-related brain changes developed problems with cognitive flexibility months before they showed signs of memory impairment. Cognitive flexibility refers to the brain’s ability to adjust behavior, learn new rules and adapt when situations change.
“We found that this function was impaired before we could detect deficits in spatial memory,” said neuroscientist Jun Wang, Ph.D., professor in the Texas A&M University Naresh K. Vashisht College of Medicine at Texas A&M Health.
Faulty calcium signaling may drive dry mouth in Down syndrome, raising gum disease risk
Researchers at NYU College of Dentistry have uncovered what may be biologically driving oral health issues unique to Down syndrome. Their study, published in Cell Reports, describes a molecular mechanism—a defect in calcium signaling—behind low saliva production, along with other factors that may contribute to gum disease.
“Understanding the processes responsible for low saliva in Down syndrome and developing therapies to restore salivation could have a transformative impact on the oral and overall health of people with Down syndrome,” said Rodrigo Lacruz, professor of molecular pathobiology at NYU College of Dentistry and the study’s senior author.
Why manufacturing is the missing link in paediatric drug discovery
As therapies grow more personalized and molecularly complex, advancing them from lab to clinic depends not only on drug discovery, but on how those drugs are made. Frank Fazio, president of the Good Manufacturing Practices (GMP) Facility at St. Jude Children’s Research Hospital in Memphis, Tennessee, explains how close integration of research and production is helping reshape paediatric drug development — and accelerating the path from discovery to patient care.
How is biological insight reshaping drug safety?
Precision has improved dramatically. As we understand the underlying biology better, we’re selecting more relevant targets and pursuing them with greater confidence. We still encounter failures, but it feels less frequent because the biology is becoming clearer.
Blood protein clocks flag higher risks of death and chronic disease
Organ-specific age gaps showed strong associations with cancers affecting the corresponding organ. The strongest association was observed between kidney biological age and renal cancer (HR, 1.6). Organ-specific aging in lungs and intestines also increased the risk of lung cancer and stomach cancer, respectively (HR, 1.4 for both). The sensitivity analysis yielded largely similar results, except for attenuations in kidney and lung cancer, indicating the robustness of the primary findings.
The Global Proteomic Aging Clock predicted mortality from any cause as accurately as conventional risk factors. Combining the findings with established risk factors further improved mortality prediction compared with using risk factors alone.
Single Injection Reverses Osteoarthritis in Animals in Just 4 Weeks
The chronic loss of joint cartilage known as osteoarthritis causes pain and bone decay for hundreds of millions of people every day.
But a new treatment option just got a step closer to human trials – in the form of a simple, single shot.
Based on ongoing animal experiments, researchers have shown that injecting a carefully engineered, slow-release drug-delivery system into the damaged joint can coax the body’s own cartilage and bone cells to carry out an effective repair job in just a few weeks.
