Jun Hung Cho, Ph.D., RAC(Drugs)’s Post

Facing Mortality: The Complex Reality of Cancer Deaths The phrase "metastasis accounts for 90% of cancer deaths" is overly simplistic and lacks primary analysis support. While metastatic disease increases mortality risk, cancer death causes are complex, involving multiple bodily systems. Insufficient detail in death certificates and incomplete recording of comorbidities, such as cachexia, hinder systematic analyses. Factors such as metastasis location, organ function disruption, molecular mediators, and patient characteristics (age, health, genetics) influence mortality. Understanding these factors can improve, enhance life quality, and guide treatment. Early palliative care improves survival, and better knowledge of advanced disease processes can reduce end-of-life suffering. This review summarizes immediate mortality causes, patient deterioration factors, and future research recommendations. It is worth reading for anyone interested in the subject. https://lnkd.in/guNgTwdu

The extensive safety data from outcome studies and real-world evidence support the use of GLP-1 medicines for people with type 2 diabetes, most of whom are also overweight or obese. These medications reduce the risk of major adverse cardiovascular events (MACE) and cardiovascular death, as well as lower the rates of chronic kidney disease in people with type 2 diabetes and many more. However, there is limited experience with these drugs in populations such as children, adolescents, the severely ill hospitalized, and the elderly. Many new GLP-1 medicines are in development, including small molecules, antibodies, and hybrid molecules that target additional signaling pathways. These new treatments will need careful evaluation to ensure they provide equal or greater benefits without introducing new safety concerns, promising an exciting future ahead. This excellent review addresses these concerns comprehensively. https://lnkd.in/eKA3s-Pu

Bispecific and multispecific antibodies offer enhanced cancer treatment by targeting multiple antigens but still face significant development challenges, including optimizing their design and manufacturing for better efficacy and safety, minimizing toxicity and off-target effects, and improving patient selection to maximize therapeutic benefits. Addressing these issues is essential for advancing their use in oncology, presenting exciting opportunities for the future. https://t.co/uk7tQoiBvJ

Revolutionizing Pathology: Machines Mastering Slide Recognition. The article explores how computational pathology has advanced through digital slide scanning, AI breakthroughs, and extensive datasets. While deep learning has revolutionized tasks like cancer diagnosis and treatment prediction, the role of natural language in pathology—leveraging medical knowledge and guiding AI development—remains largely untapped. The rise of multimodal large language models (MLLMs) is poised to bridge this gap by integrating natural language processing with visual data, potentially transforming clinical decision-making, research, and medical education in pathology. https://lnkd.in/eytN6KxY https://rdcu.be/dKC0r https://lnkd.in/e4hDk7kk https://lnkd.in/eV-sPSU3

### Breakthrough Discovery: Undisturbed Image Sorting Reveals How T Cells Decide Fate in Viral Infections. This exciting paper revealed how naïve T cells decide to become effector or memory T cells during viral infections, crucial for long-term immunity. Using self-supervised deep learning for image processing, they identified three T cell classes: polarized (Tp), conventional spherical (To), and "stripy" spherical (Tø) with unique nuclear envelope invaginations forming organelle factories. During viral infection, T cells shift from Tø to Tp in the effector phase and revert to Tø in memory cells after 28 days. Tø cells show stronger TCR signaling and form large effector colonies, while To cells divide slower and become memory-like. These findings underscore the role of T cell architecture and advanced image processing in determining cell fate, offering potential improvements in infection protection and undisturbing sorting of effective cells for disease treatment. http://bit.ly/stripyBH

At the recent Computex in Taipei, Jensen Huang, CEO of NVIDIA, highlighted the transformative potential of advanced computing technologies, emphasizing their critical role in addressing many complex challenges in fields including biomedical engineering. This aligns with the emerging field of cancer engineering, which applies engineering principles to tackle cancer-specific challenges such as altered cell metabolism, immune evasion, and resistance to cell death. Innovations in cancer imaging, drug delivery, and tissue engineering etc fall under this domain. Establishing dedicated cancer engineering centers and tailored training programs is essential to foster collaboration among biologists, engineers, and clinicians, driving innovation in targeted cancer therapies and improving patient outcomes. https://lnkd.in/e_Wrj32C https://lnkd.in/eDARhmd7

Chimeric antigen receptor (CAR) T cell therapy is a groundbreaking immunotherapy, particularly effective in refractory hematologic malignancies. The manufacturing process significantly impacts clinical outcomes, necessitating flexible and efficient good manufacturing practice (GMP) strategies as demand grows. The development of new products requires robust assay development and quality control to ensure consistency and safety. However, a major challenge is the global shortage of skilled manufacturing staff, with labor-intensive processes contributing significantly to production costs. This review explores advancements in CAR-T manufacturing, highlighting innovations that could enhance product quality and accessibility. https://lnkd.in/ePJQJDzt

Antibody-based therapeutics hold significant promise in oncology due to their remarkable precision in targeting specific cancer cells. This capability allows for more effective treatments, potentially reducing harm to healthy cells and improving patient outcomes. Despite major challenges, such as the complexity of cancer biology and resistance development, researchers are identifying new targets and developing novel designs and engineering strategies to overcome these issues. The past 25 years have seen a surge in regulatory approvals for effective antibody-based therapeutics, a trend likely to continue as advancements in biotechnology and a deeper understanding of cancer mechanisms drive further progress. This excellent review examines their mechanisms of action, the structural basis for target specificity, clinical applications, and different approaches upon ongoing research aimed at improving efficacy and reducing toxicity. https://lnkd.in/ewS3-KpF

The mRNA vaccines offer a promising avenue for advancing cancer immunotherapy, building on the early insights of William Coley in the late 1800s. Despite a history of challenges with traditional cancer vaccines, the advent of mRNA technology, accelerated by initiatives like Operation Warp Speed during the COVID-19 pandemic, has led to significant advancements. These vaccines, leveraging mRNA encoding tumor antigens, hold potential for eliciting robust and adaptable immune responses against cancer. This review explores the evolution of mRNA-based cancer vaccines, from their development and delivery methods to ongoing clinical trials and future prospects. https://lnkd.in/g4jF8Gx2

Interesting GLP paper: The N-methyl-D-aspartate (NMDA) receptor, crucial for brain functions, is implicated in body weight regulation, as indicated by genome-wide association studies. The Novo Group of scientists present the development of a bimodal compound merging NMDA receptor antagonism with glucagon-like peptide-1 (GLP-1) receptor agonism, effectively tackling obesity, hyperglycemia, and dyslipidemia in rodent models of metabolic disease. By targeting MK-801, an NMDA receptor antagonist, to GLP-1 receptor-expressing brain regions,this approach enhances neuroplasticity in the hypothalamus and brainstem while avoiding adverse effects linked to MK-801 monotherapy. This strategy showcases the potential of peptide-mediated targeting for precise ionotropic receptor modulation, offering a safe and potent avenue for combating obesity. https://lnkd.in/gd4pQBSZ