Limited epidemiologic evidence links cancer risk to dietary acid load and methionine intake. Acid stress and metabolic acidosis are closely related to cancer development. Methionine is the main acidogenic amino acid and exerts epigenetic influences. We recently reported preliminary results on dietary acid load, methionine intake, and breast cancer risk. Therefore, both variables deserve further epidemiologic analysis. We revisited a Uruguay-based case-control study (572 cases/2,294 matched controls); women were recruited from 4 central hospitals, and all were interviewed using a specific questionnaire. Food-derived nutrients were calculated from available databases. Dietary acid load was estimated based on a validated formula: the potential renal acid load (PRAL) score. OR was estimated by logistic regression, adjusting for potential confounders. We found significant, direct associations between the breast cancer risk and PRAL (OR = 3.33) and methionine intake (OR = 5.87). Trends were significant (P < 0.001).PRAL and methionine displayed higher ORs among subsets with a positive family history of cancer compared to a negative one:OR = 6.16 vs. 2.80 (PRAL); OR = 11.8 vs. 4.86 (methionine). Both estimates were higher in pre- than postmenopausal women: OR = 5.91 vs. 2.96 (PRAL); OR = 8.76 vs. 5.39 (methionine). In conclusion, an acidogenic dietary style may increase a breast cancer risk. Furthermore, our findings suggest that methionine intake, showing comparable or even higher ORs than the dietary acid load scores themselves, might influence the risk associated with acid-base imbalance, ultimately leading to cancer. Additional research on methionine-induced epigenetic influences is warranted.

Estrogen receptor alpha (ERα) defines the biology of estrogen receptor-positive breast cancer by regulating both tumor-intrinsic signaling and the surrounding immune microenvironment. Beyond its genomic and non-genomic actions, ERα modulates cytokine production, antigen presentation, and the activity of innate and adaptive immune cells, contributing to a low mutational burden, weak immunogenicity, and an immune-excluded tumor state. Through interactions with NF-κB, suppression of interferon pathways, and regulation of myeloid and lymphoid cell functions, ERα promotes immune tolerance and supports tumor progression. These immunoregulatory effects help explain limited responses to endocrine therapy and the poor performance of immune checkpoint inhibitors in ER-positive diseases. Emerging strategies, including next-generation selective estrogen receptor degraders and combinations with CDK4/6 inhibitors or immunotherapy, aim to overcome ERα-driven immune suppression. Understanding ERα-mediated immune regulation will be essential for developing more effective therapeutic approaches for ER-positive breast cancer.

Lung cancer remains one of the most prevalent and lethal malignancies worldwide. Most cases are caused by non-small-cell lung cancer (NSCLC). Over the past three decades, the treatment landscape of NSCLC has been profoundly reshaped by the discovery of epidermal growth factor receptor (EGFR) mutations and the subsequent development of EGFR-targeted therapies. This review provides a comprehensive overview of the evolution of four generations of EGFR tyrosine kinase inhibitors (EGFR-TKIs): first-generation reversible inhibitors such as gefitinib and erlotinib; second- and third-generation irreversible inhibitors, including afatinib, dacomitinib, and osimertinib; and emerging fourth-generation agents, such as amivantamab. Each generation has contributed to efficacy improvement, central nervous system penetration, and resistance management. Despite remarkable advances in development of EGFR-TKIs, acquired resistance and tumor heterogeneity remain major challenges. Bioinformatic analyses using The Cancer Genome Atlas (TCGA) datasets highlight the high mutation frequency and clinical significance of EGFR alterations, underscoring their pivotal role in tumor progression and prognosis. Future studies should explore combination therapies, antibody–drug conjugates, and next-generation allosteric inhibitors as promising strategies to overcome resistance. The evolution of EGFR-targeted therapy exemplifies the progress of precision oncology and serves as a basis for designing new paradigms in the management of lung cancer.

suggest that some reproductive factors associated with BC differ across ethnicities and time trends, perhaps due to the prevalence of reproductive factors and the baseline hazard of BC.

This study aimed to determine the association between trajectories of obesity status and prediabetes reversion to normoglycemia or progression to diabetes. The study included 14,452 participants from the National Health Insurance Service-National Health Screening (NHIS-HEALS) cohort who continuously had prediabetes glycemic status during the index period (2002-2008), definedby their fasting plasma glucose. The exposure of the study was the trajectories of obesity (defined by body mass index ≥ 25 kg/m 2 ) generated using latent class growth analysis. The outcomes were reversion to normoglycemia or progression to diabetes, whichever occurred first during the follow-up period (2009-2016). The association between trajectories and changes in prediabetes status were examined using cause-specific hazard regression by obtaining the hazard ratio (HR) with a 95% CI. We identified three distinct trajectories which were “Stable obese”, “Stable non-obese” and “Obese to non-obese”. After a median follow-up of 2years, 51.99% of participants had their glycemic status back to normoglycemia and 32.17% developed diabetes. Compared with participants in the “Stable obese” group, those in “Stable non-obese” and “Obese to non-obese” groups were more likely to have reversion to normoglycemia (HR with a 95% CI = 1.30 [1.23-1.37] and 1.15 [1.07-1.24], respectively) and lower risk of developingdiabetes (0.78 [0.73-0.84] and 0.90 [0.82-0.98], respectively). The findings suggest that maintaining or achieving a non-obese sta-tus is linked to higher reversion to normoglycemia as well as lower risks of developing diabetes.

Due to rapid westernization, Korean dietary habits have emerged as significant risk factors for chronic disease and cancer. Despite this transition, Korea’s cancer prevention guidelines have remained consistent since their establishment about 18 years ago. This study aimed to investigate the degree of awareness and practice to global dietary guidelines among Korean adults and identify demographic and lifestyle factors associated with low practice. A cross-sectional survey conducted in 2023 included 4,000 adults and assessed their awareness and practice of four global recommendations: “Eat a diet rich in whole grains,” “Limit consumption of processed meat,” “Limit consumption of sugar-sweetened beverages,” and “Limit consumption of fast and other processed foods.” While more than half of the participants recognized the guidelines’ importance for cancer prevention, implementation rates remained below 40%. Furthermore, over 80% of the respondents expressed a compelling requirement for updated and tailored dietary guidelines. Younger individuals, those who were physically inactive, individuals who had not received prior nutrition education, and participants with obesity were more likely to exhibit low practice, particularly to guidelines limiting processed foods and sugary beverages intake. These findings highlight the need to revise Korea’s cancer prevention recommendations by incorporating global dietary practices and addressing the westernized eating patterns prevalent within the population. Efforts should focus on promoting these updated guidelines through targeted education and public health interventions that improve practice, especially in high-risk groups, and effectively mitigate the burden of diet-related cancers in Korea.

Chromosomal alterations are frequent events in lung cancer progression. Although gains and losses of chromosomal position have been reported, the association between copy number alteration and lung cancer patient survival has not been extensively investigated. In this study, we performed a meta-analysis of public cBioPortal datasets spanning 25 lung cancer studies to identify putative cancer driver genes with copy number alterations associated with overall patient survival. Ten copy-number altered genes enriched in deceased lung cancer patients were identified. Seven of these putative driver genes were located in the 7p11.2 chromosomal location, and two were in the 9p21.3 cytoband. Among these genes, the mitochondrial ribosomal protein S17 (MRPS17) amplification was significantly associated with a lower patient survival rate (P = 1.47e-7). To investigate the functional role of MRPS17, small interfering RNA-mediated knockdown was performed in two non-small cell lung cancer cell lines, A549 and NCI-H460. MRPS17 knockdown significantly reduced cell proliferation, migration, invasion, and anchorage-independent growth in both cell lines. Furthermore, knockdown of MRPS17 decreased the activation of the phosphatidylinositol 3-kinase/protein kinase B signaling pathway, suggesting its role in driving lung cancer progression through this critical oncogenic pathway. Our findings highlight MRPS17 as a potential cancer therapy target and a prognostic biomarker that may improve the survival rates of lung cancer patients. Future studies should explore its inhibition as a therapeutic strategy as well as elucidate its molecular mechanisms in cancer progression.

Renal cancer continues to offer a great challenge for its successful therapy today, thus underscoring the need for effective chemotherapeutic agents. In the current study, we explored the anticancer effects of domperidone, a dopamine D2 receptor (DRD2) antagonist, in renal cancer Caki-2 cells. Domperidone induced dose and time-dependent cytotoxic effects in Caki-2 cells, triggering intrinsic apoptosis via the stimulation of the caspase cascade and PARP cleavage. The cytotoxic effect of domperidone was found to be partially DRD2-dependent. Domperidone treatment markedly augmented the production of intracellular reactive oxygen species which induced the cell death of Caki-2 cells. In addition, domperidone suppressed Janus kinase 2 and STAT3 phosphorylation, leading to inhibition of survival and proliferation of these cells. Hence, domperidone can be considered a promising candidate for renal cancer treatment.

Breast cancer is the most common cancer among women worldwide, with germline mutations in high-penetrance genes like BRCA1 and BRCA2, and moderate-penetrance genes such as CHEK2 and ATM contributing majorly to the onset of the same.Universal germline genetic testing offers an avenue to improve early identification and develop appropriate management guidelines. Our retrospective cohort study analyzed data from 525 newly diagnosed breast cancer patients at Mercy Hospital Fort Smith from January 2020 to December 2023. Patients underwent germline genetic testing using next-generation sequencing panels irrespective of family history of cancer. Details on patient demographics, clinical characteristics, and genetic test results were collected and analyzed. The median age at diagnosis of patients was 66, with invasive ductal carcinoma (IDC) being the major subtype (66%). CHEK2 mutations were the most common pathogenic mutations (9 patients), followed by BRCA1 and MUTYH (6 each).Pathogenic mutations were more prevalent in patients over 60 years (63%). Germline mutations were identified more frequently in IDC than in ductal carcinoma in situ. Among patients with germline mutations, there was a significant drift toward mastectomy over breast-conserving surgery. Universal germline genetic testing identified pathogenic mutations in a significant proportion of breast cancer patients, especially among the older patient population. The findings further emphasize the importance of integrating universal genetic testing into routine care to guide surgical and risk-reduction management protocols effectively. Further research is needed to regularize genetic testing in similar patients.