The mechanisms of epidermal growth factor (EGF) affecting EGF receptor inhibitor (EGFRI)-related skin toxicities are as yet unknown. We investigated which mechanisms are involved in EGF’s positive effects. Two types of EGFRIs, cetuximab and gefitinib, were used to treat the cells or 3d-cultured human skin tissue with recombinant human EGF (rhEGF). As a result, rhEGF increased EGFR and pEGFR expression. Furthermore, rhEGF induces EGFR signaling by pAKT and pPI3K expression in gefitinib and rhEGF co-treated cells. In addition, rhEGF bound to EGFR after than cetuximab, but cetuximab bound to EGFR more strongly than rhEGF. Moreover, expressions of proliferation and differentiation proteins, both ki-67 and filaggrin, were decreased in EGFRI-treated tissue. However, in rhEGF and EGFRI co-treated tissue, those expressions were increased. Expression of IL-1α, IL-8, and TNF-α was increased by EGFRIs and down-regulated by rhEGF. Furthermore, hBD-2 and hBD-3 protein expressions were inhibited by cetuximab or gefitinib treatment, and those decrements were increased by rhEGF treatment. In patients’ tissue evaluation, compared with controls, patients’ Ki-67 and EGFR expression were decreased (p = 0.015, p = 0.001). Patients’ IL-17 and TNF-α expression intensity was higher than that of the control group (p = 0.038, p = 0.037). After treatment with EGF ointment, average values of Ki-67, EGFR, and Melan-A were changed to normal values. Oppositely, patients’ proportions of IL-17 and TNF-α were decreased to low stain level. In conclusion, treatment of rhEGF improved EGFRI-induced skin eruption via normalizing the proliferation and differentiation of keratinocytes, reducing inflammatory cytokines by the affected EGFRIs.

Background: With the development of immunology, immune checkpoint inhibitors (ICIs) have been widely used in various cancer treatments. Although some patients can benefit from ICIs, other patients have no response to ICIs or suffer from hyperprogression. There has been no biomarker for predicting the efficacy of ICIs. Thus, the objective of this study was to find biomarkers for predicting the efficacy of ICIs using peripheral blood. Methods: Adults patients planned to be treated with ICIs were enrolled in this study. Blood sampling was carried out before and after administration of ICIs. Changes of immune cell fraction were analyzed for each patient. Results: Among 182 patients enrolled, immune cell analysis was performed for 90 patients. The objective response rate was 14.4% (n = 13/90). The median progression-free survival (PFS) was 6.0 months (95% CI: 3.1–8.9 months), and the median overall survival (OS) was 13.9 months (95% CI: 5.6–22.2 months). Significant benefits in ORR and OS were shown for patients with increased NKp46-/CD56+ NK cells (p = 0.033 and p = 0.013, respectively). The PFS tended to be longer in these patients, although the difference was not statistically significant (p = 0.050). Conclusion: Changes of immune cell fraction before and after administration of ICIs could be a novel biomarker for predicting the efficacy of immunotherapy.

Background: Although insulin resistance has been implicated in cancer development, its specific role in lung cancer remains unclear. The metabolic score for insulin resistance (METS-IR) is a novel surrogate marker that integrates multiple metabolic parameters and has demonstrated strong predictive value for metabolic disorders. This study aimed to investigate the association between METS-IR and lung cancer incidence in a large-scale nationwide cohort. Methods: We analyzed data from 322,624 participants of the National Health Insurance Service-National Health Screening Cohort in Republic of Korea. Participants were stratified into METS-IR quartiles, and lung cancer incidence was assessed using Kaplan–Meier survival curves and Cox proportional hazards regression models. Subgroup analyses were conducted to examine the impact of body composition, particularly sarcopenia, on the association between METS-IR and lung cancer. Results: Over a median follow-up of 9.5 years, 5912 lung cancer cases were identified. Lung cancer incidence per 1000 person-years was highest in the lowest METS-IR quartile (Q1: 2.27) and decreased across quartiles (Q2: 1.93, Q3: 1.81, Q4: 1.72). In fully adjusted Cox regression models, using Q1 as the reference group, higher METS-IR quartiles were associated with a significantly lower risk of lung cancer (Q2: HR 0.91, 95% CI 0.85–0.98; Q3: HR 0.86, 95% CI 0.79–0.92; Q4: HR 0.80, 95% CI 0.74–0.86; p for trend < 0.001). Subgroup analyses revealed that the inverse association was more pronounced in male participants and individuals with a low body mass index. Conclusions: In this nationwide cohort study, we observed a significant inverse association between METS-IR and lung cancer risk. However, METS-IR showed limitations in fully explaining lung cancer risk based on insulin resistance alone. These findings highlight the need for future studies incorporating body composition assessments to better evaluate metabolic vulnerability.

Maeng CH, et al. J Korean Med Sci. 2027 Mar;42:e57. https://doi.org/10.3346/jkms.2027.42.e57