Current Pharmaceutical Design - Online First

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) has become a worldwide health crisis. In addition to its effects on liver function, MASLD intensely increases the risk of hepatocellular carcinoma (HCC) and a number of extrahepatic cancers, including breast, colorectal, and pancreatic cancers. This review explores the complex network of molecular pathways linking MASLD to cancer, emphasizing the involvement of oxidative stress, lipotoxicity, insulin resistance, chronic inflammation, and mitochondrial dysfunction. Genetic variations in important genes, including PNPLA3, TM6SF2, and MBOAT7, increase this risk by hastening the course of the disease and making a person more susceptible to cancer. By shedding light on these important pathways and genetic factors, this research not only advances knowledge of the relationship between MASLD and cancer but also opens the door for novel treatment approaches meant to reduce the risk of cancer in MASLD patients. Millions of people afflicted by this deadly but silent illness may benefit from novel therapies that target these fundamental systems.

Liver cancer, particularly Hepatocellular Carcinoma (HCC), remains a significant global health challenge owing to its high incidence and position as the fourth leading cause of cancer-related mortality. HCC represents 75-85% of all liver cancer cases and ranks as the sixth most prevalent cancer globally. Several factors, including late-stage diagnosis, limited treatment effectiveness, resistance to conventional therapies, and adverse side effects, hinder the delivery of life-prolonging care to patients with HCC. Current treatment options such as chemotherapy, immunotherapy, and adjuvant therapy are often associated with severe side effects. Consequently, there is an urgent need for improved diagnostic methods and alternative therapeutic approaches to extend life expectancy and reduce HCC-related mortalities. Artificial Intelligence (AI) is an emerging technology that offers promising advances for the early detection of HCC. In terms of alternative treatments, natural compounds have garnered significant attention because of their diverse biological activities, such as antitumor, antiviral, antimicrobial, antioxidant, anti-inflammatory, hepatoprotective, antimutagenic, and cardioprotective effects, and their relatively lower side effect profiles. These compounds exhibit hepatoprotective properties by modulating key molecular pathways involved in HCC development and progression. This article provides an overview of recent advances in the understanding of liver cancer etiology, therapeutic targets in HCC pathogenesis, the role of AI in its detection, and the potential of natural products, particularly flavonoids, as preventive and therapeutic agents against HCC, highlighting their underlying mechanisms of action.

Amyloid beta (Aβ) dyshomeostasis is considered the main biological aberration in Alzheimer’s Disease (AD) pathology. The interplay between Aβ formation and clearance is predominantly modulated by a disintegrin and a metalloproteinase 10 (ADAM10, α-secretase) and β-site APP Cleaving Enzyme 1 (BACE1), the two pivotal enzymes in both non-amyloidogenic/amyloidogenic and amyloidolytic pathways. Emerging evidence suggests that aberrations in ADAM10 and BACE1 expression, activity, and function in the brain of AD patients also manifest in peripheral fluids, suggesting their potential as blood-based biomarkers for AD diagnosis. This review provides a comprehensive overview of the literature by exploring the roles of ADAM10 and BACE1 in AD, spanning from their involvement as pathological AD drivers to their potential utility as promising biomarkers.

Polymer and lipid-based nanocarriers are a state-of-art in nanomedicine and in co-drug delivery of drugs that could merges various diagnostic and treatment modalities such radiotherapy (RT), photodynamic therapy (PDT) and chemotherapy (CT) in cancer therapy. Among various shapes and nanostructures, polymer and lipid-based nanocarriers have the potential to carry two drugs in same time to cells. However, hydrophobic and hydrophilic drug can be loaded in between layers as well as in the core of these nanocarriers, simultaneously. This advantage of NPs can be employed in combination therapy. Radiosensitizer and photosensitizer agents play a critical role in radio-photodynamic therapy (RT-PDT) of cancer. Co-delivery of these agents to cancerous cells is advantageous to cancer therapy but still remain as a challenge of RT-PDT. However, in this review, we have highlighted the challenges of RT-PDT and role of polymer and lipid-based nanocarriers to co-delivery of hydrophobic and hydrophilic agents as radio-photosensitizers. Hence, the different kinds of Poly (lactic-co-glycolic acid) nanoparticles (NPs) have been categorized. Then, the biophysical mechanism of radio-photosensitizer agents with co-loading on polymer and lipid-based nanocarriers in RT-PDT treatment of cancer has been outlined. Finally, attention has been drawn to polymer and lipid-based nanocarriers in co- drugs delivery. Taken together, this work presents the latest updates on this area and highlighted the pros and cons of co-delivery for RT-PDT purposes.