A comprehensive review reveals that blocking natural killer cell checkpoints and employing precision strategies like gene editing and engineered cell therapies could significantly enhance cancer immunotherapy outcomes for solid tumors and blood cancers.

Phosphatases have long been considered undruggable, but recent discoveries are changing that perception. Compared to kinases, phosphatases remain underexplored in cancer therapy, despite their critical roles in tumour progression. Dysregulated phosphatases drive tumour growth, metastasis, angiogenesis, immune evasion, therapy resistance, and intracellular communication—through the modulation of oncogenic signaling pathways.

Phosphatases are governed by a complex regulatory system that must be understood to develop effective targeted therapies. However, phosphatases could be broadly categorized as tumour promoters, tumour suppressors, or having dualistic functions.

This review explores the roles of various phosphatases in cancer cells and immune tumour microenviroment, with a focus on their signaling mechanisms and the current latest therapeutic strategies.

The study investigates the interaction between the human epidermal growth receptor 2 (HER2) and amygdalin, a compound found in peaches, almonds, and apples. To assess the potential of amygdalin, the interaction between HER2 and amygdalin was explored using molecular docking and molecular dynamics simulations. Binding energies were evaluated for both the crystal and equilibrated HER2 structures. The effects of water on binding were also assessed. Molecular dynamics simulations analyzed structural changes in HER2, including interdomain distances, hydrogen bond fluctuations, dihedral angle shifts, and residue-residue distances at the dimerization arm. The free energy landscape was constructed to evaluate stability. Binding energies of −33.472 ​kJ/mol and −36.651 ± 0.867 ​kJ/mol were observed for the crystal and equilibrated HER2 structures, respectively, with water further enhancing binding to −41.212,4 ​± ​1.272,7 and −53.513 ± 1.452,3 ​kJ/mol. Molecular dynamics simulations revealed significant conformational changes in HER2, including a reduction in interdomain distance, fluctuations in hydrogen bond lengths, and a shift in dihedral angles from 60° to −30°. The residue-residue distance at the dimerization arm decreased, indicating conformational changes upon binding. The free energy landscape showed a deeper and more defined minimum in the bound state, reflecting enhanced stability. These findings highlight amygdalin’s potential as a therapeutic agent targeting HER2.

A recent study published in Genes & Diseases explores the clinical implications of loss-of-function mutations in IKBKG/NEMO, a key regulator in the NF-κB signaling pathway. These mutations are linked to a range of rare and often severe genetic disorders, including Incontinentia Pigmenti (IP), Anhidrotic Ectodermal Dysplasia with Immunodeficiency (EDA-ID), Immunodeficiency (ID), and NEMO Deleted Exon 5 Autoinflammatory Syndrome (NDAS). The research aims to provide a comprehensive review of the diverse clinical manifestations associated with mutations in the IKBKG gene, highlighting the genotype-phenotype correlation that has remained elusive due to the variability in IKBKG mutations.

A groundbreaking study published in Genes & Diseases has revealed that exogenous pyruvate significantly alleviates the symptoms of ulcerative colitis (UC) by targeting cytosolic phospholipase A2 (cPLA2). This discovery opens new avenues for the treatment of UC, which remains a chronic inflammatory bowel disease with limited therapeutic options. The study shows that pyruvate can suppress the TNFα/NFκB signaling pathway, which is pivotal in driving inflammation, thereby offering a novel approach to mitigating UC symptoms.

A recent study published in Genes & Diseases reveals new insights into the relationship between immune cell characteristics, blood metabolites, and the risk of urolithiasis. Using Mendelian randomization (MR) and mediation analysis, the research highlights how genetically predicted blood metabolites mediate the association between specific immune cell profiles and the development of urinary stones. The findings shed light on potential pathogenic mechanisms and suggest novel therapeutic targets for this widespread and recurrent condition.

A recent study published in Genes & Diseases has unveiled a novel mechanism by which the restriction of YWHAB-mediated YAP cytoplasmic retention plays a crucial role in maintaining stemness and chemoresistance in ovarian cancer peritoneal metastasis (OCPM). Researchers have found that the down-regulation of YWHAB in OCPM cells promotes the activation of YAP signaling, enhancing the cancer cells' ability to resist chemotherapy and maintain stem-like characteristics. This discovery may lead to innovative therapeutic strategies targeting the YWHAB-YAP pathway to combat the high mortality associated with ovarian cancer metastasis.