Alzheimer’s disease (AD) and type 2 diabetes mellitus (T2DM) are two prevalent conditions that present considerable public health issue in aging populations worldwide. Recent research has proposed a novel conceptualization of AD as “type 3 diabetes”, highlighting the critical roles of insulin resistance and impaired glucose metabolism in the pathogenesis of the disease. This article examines the implications of this association, exploring potential new avenues for treatment and preventive strategies for AD. Key evidence linking diabetes to AD emphasizes critical metabolic processes that contribute to neurodegeneration, including inflammation, oxidative stress, and alterations in insulin signaling pathways. By framing AD within this metabolic context, we can enhance our understanding of its etiology, which in turn may influence early diagnosis, treatment plans, and preventive measures. Understanding AD as a manifestation of diabetes opens up the possibility of employing novel therapeutic strategies that incorporate lifestyle modifications and the use of antidiabetic medications to mitigate cognitive decline. This integrated approach has the potential to improve patient outcomes and deepen our comprehension of the intricate relationship between neurodegenerative diseases and metabolic disorders.

The global prevalence of type 2 diabetes mellitus (T2DM) necessitates the exploration of novel therapeutic approaches to mitigate its complex molecular pathogenesis. This review investigates the potential role of genistein, a prominent isoflavone derived from soybeans, in the management of T2DM. Recognized for its selective estrogen receptor modulator (SERM) activity, genistein exerts a multifaceted influence on key intracellular signaling pathways, which are crucial in regulating cell proliferation, apoptosis, and insulin signaling. Genistein’s anti-inflammatory, anti-oxidant, and metabolic regulatory properties position it as a promising candidate for T2DM intervention. This review synthesizes current research spanning preclinical studies and clinical trials, emphasizing genistein’s impact on insulin sensitivity, glucose metabolism, and inflammatory markers. Additionally, this review addresses genistein’s bioavailability, safety, and potential influence on gut microbiota composition. By consolidating these findings, this review aims to provide a comprehensive understanding of genistein’s therapeutic potential in T2DM management, offering valuable insights for future research and clinical practice.

The PD-1/PD-L1 pathway has emerged as a critical target in colorectal cancer (CRC) immunotherapy, with pembrolizumab, nivolumab, and dostarlimab demonstrating significant clinical efficacy, particularly in microsatellite instability-high (MSI-H) and mismatch repair-deficient (dMMR) tumors. However, a growing number of additional PD-1/PD-L1 inhibitors, including AMP-224, atezolizumab, avelumab, camrelizumab, durvalumab, envafolimab, sintilimab, spartalizumab, tislelizumab, and toripalimab, are currently under investigation, offering new possibilities for the expansion of treatment options. This review evaluates the therapeutic potential of these emerging agents, assessing their clinical development, mechanisms of action, and potential advantages over established therapies. Additionally, it explores key challenges such as primary and acquired resistance, limited efficacy in microsatellite-stable (MSS) CRC, and the complexities of combination strategies aimed at enhancing immunotherapeutic responses. By addressing these obstacles and highlighting prospects, this review provides insights into the evolving landscape of PD-1/PD-L1-targeted therapies in CRC and their potential to improve patient outcomes.

Pancreatic cancer (PC) remains a highly lethal malignancy with limited treatment options and poor survival. Targeting DNA damage response (DDR) pathways has emerged as a promising therapeutic strategy, particularly the ATR-CHK1 and ATM-CHK2 axes. Preclinical studies demonstrate that ATR inhibition disrupts replication stress tolerance, impairs homologous recombination, and disables checkpoint control, enhancing cytotoxicity from standard therapies including gemcitabine, FOLFIRINOX, fluoropyrimidines, and radiotherapy. Synergistic effects have also been observed with other DDR-targeted agents, such as PARP and WEE1 inhibitors. Genomic contexts, including ATM deficiency, ARID1A alterations, and oncogene-driven replication stress, refine therapeutic sensitivity, supporting precision patient stratification. Early-phase clinical trials of ATR inhibitors (ART0380, AZD6738, BBI-355) alone or in combination show promising safety, tolerability, and preliminary efficacy. In this review, we summarize current literature on targeting the ATM-CHK2 and ATR-CHK1 pathways in PC, highlighting preclinical evidence, clinical developments, and strategies for biomarker-driven, precision oncology approaches.

Oxeiptosis is a reactive oxygen species (ROS)-dependent form of programmed cell death that plays a key role in cellular homeostasis and holds promise as a cancer therapy. This review explores its molecular mechanisms, emphasizing the KEAP1–PGAM5–AIFM1 signalling pathway and its reliance on ROS accumulation. Compared to other cell death pathways, oxeiptosis offers a distinct approach, especially for targeting cancer cells resistant to conventional therapies. The review evaluates emerging inducers, both synthetic and natural, that selectively trigger oxeiptosis in cancer cells. It also examines the potential synergy between oxeiptosis and ROS-generating chemotherapies, particularly in the oxidative tumour microenvironment. However, challenges remain, including identifying tumour-specific inducers, overcoming cancer cell resistance to oxidative stress and reducing off-target effects. The review concludes by highlighting the need for targeted delivery strategies and rigorous preclinical studies to translate oxeiptosis into effective cancer treatments. Overall, it underscores oxeiptosis as a promising avenue to address drug resistance and improve therapeutic outcomes in oncology.

Licofelone is a 1H-pyrrolizine carboxylic acid based dual COX/5-LOX inhibitor, emerges as a promising therapeutic candidate due to its ability to simultaneous interference of both inflammatory pathways, but its clinical translation is restricted by its poor pharmacokinetics. The current research aims to design novel 1H-pyrrolizine carboxylic acid derivatives with the intent to improve the pharmacokinetics and explore their anticancer potential. The docking analysis of the designed analogues showed potent binding with COX-2, 5-LOX and some other anticancer targets, especially indoleamine 2,3-dioxygenase-1 (IDO1), in comparison with parent molecule. A synthetic procedure was developed and optimised for the synthesis of designed compounds followed by assessing their anticancer potential by performing an MTT assay. The obtained results have concluded that the designed licofelone-derived pyrrolizine analogues revealed that structural modifications with different amino acid conjugates significantly influenced their anticancer activity with compound 8b and 8c exhibited the most potent antiproliferative activity against PANC-1 cells with IC50 values of 1.7 ± 0.2 µM and 1.4 ± 0.05 µM, respectively. These molecules can be further used to develop novel anticancer therapeutics post preclinical and clinical validation.