Phytochemicals are natural plant-derived products that provide significant nutrition, essential biomolecules, and flavor as part of our diet. They have long been known to confer protection against several diseases via their anti-inflammatory, immune-regulatory, anti-microbial, and several other properties. Deciphering the role of phytochemicals in the prevention, inhibition, and treatment of cancer—unrestrained cell proliferation due to the loss of tight regulation on cell growth and replication—has been the focus of recent research. Particularly, the immunomodulatory role of phytochemicals, which is pivotal in unchecked cell proliferation and metastasis, has recently been studied extensively. The immune system is a critical component of the tumor microenvironment, and it plays essential roles in both preventing and promoting oncogenesis. Immunomodulation includes stimulation, amplification, or inactivation of some stage(s) of the immune response. Phytochemicals and their products have demonstrated immune regulation, such as macrophage migration, nitric oxide synthase inhibition, lymphocyte, T-cell, and cytokine stimulation, natural killer cell augmentation, and NFκB, TNF, and apoptosis regulation. There is a dearth of extensive accounts of the immunomodulatory effects of phytochemicals in cancer; thus, we have compiled these effects with mechanistic aspects of dietary phytochemicals in cancer, highlighting promising candidates and ongoing clinical trials on immunotherapeutic strategies to mitigate oncogenesis.

The consumption of the non-steroidal anti-inflammatory drug (NSAID) aspirin is associated with a significant reduction in the risk of developing TMPRSS2-ERG (fusion)-positive prostate cancer (PCa) compared to fusion-negative PCa in population-based case–control studies; however, no extensive preclinical studies have been conducted to investigate and confirm these protective benefits. Thus, the focus of this study was to determine the potential usefulness of aspirin and another NSAID, naproxen, in PCa prevention, employing preclinical models of both TMPRSS2-ERG (fusion)-driven (with conditional deletion of Pten) and non-TMPRSS2-ERG-driven (Hi-Myc^+/− mice) PCa. Male mice (n = 25 mice/group) were fed aspirin- (700 and 1400 ppm) and naproxen- (200 and 400 ppm) supplemented diets from (a) 6 weeks until 32 weeks of Hi-Myc^+/− mice age; and (b) 1 week until 20 weeks post-Cre induction in the fusion model. In all NSAID-fed groups, compared to no-drug controls, there was a significant decrease in higher-grade adenocarcinoma incidence in the TMPRSS2-ERG (fusion)-driven PCa model. Notably, there were no moderately differentiated (MD) adenocarcinomas in the dorsolateral prostate of naproxen groups, and its incidence also decreased by ~79–91% in the aspirin cohorts. In contrast, NSAIDs showed little protective effect against prostate tumorigenesis in Hi-Myc^+/− mice, suggesting that NSAIDs exert a specific protective effect against TMPRSS2-ERG (fusion)-driven PCa.

Sickle cell disease (SCD) is an autosomal recessive hemoglobin disorder that is mainly characterized by the presence of hemoglobin S (HbS; point mutation [Glu6Val] in the beta-globin gene). Under deoxygenated conditions, HbS polymerizes and serves as the primary trigger of oxidative stress in red blood cells (RBCs), promoting polymerization of Band 3, a major membrane scaffold protein that links the lipid bilayer to the spectrin–ankyrin cytoskeletal network. Phosphorylation at key residues within the cytosolic domain of Band 3 induces conformational changes that weaken ankyrin binding and enhance lateral mobility and clustering of Band 3. These effects are mediated through a coordinated network of erythrocyte tyrosine kinases, primarily spleen tyrosine kinase (SYK) and sarcoma (Src) family kinases, which act sequentially to modify distinct tyrosine residues. Structural features of these kinases, including tandem SH2 domains in SYK and conserved SH2–SH3–kinase domain architecture of Src family members, enable precise recognition of phosphotyrosine motifs and propagation of phosphorylation cascades. Sequence alignment and structural superimposition of SH2 domains across studied kinases demonstrate a highly conserved fold that is critical for phosphotyrosine recognition, suggesting potential overlap in substrate engagement. Therapeutically, targeting these kinases has shown considerable promise, as tyrosine kinase inhibitors (TKIs) reduce Band 3 phosphorylation, restore RBC deformability, and decrease hemolysis and vaso-occlusive interactions in vitro. Thus, in this narrative review, we focus on the regulation of Band 3 by the above-mentioned tyrosine kinases, as well as the therapeutic potential of TKIs in SCD.