Novel cancer treatment paradigm targeting hypoxia-induced factor in conjunction with current therapies to overcome resistance.

Chemotherapy, radiotherapy, targeted therapy, and immunotherapy are established cancer treatment modalities that are widely used due to their demonstrated efficacy against tumors and favorable safety profiles or tolerability. Nevertheless, treatment resistance continues to be one of the most pressing unsolved conundrums in cancer treatment. Hypoxia-inducible factors (HIFs) are a family of transcription factors that regulate cellular responses to hypoxia by activating genes involved in various adaptations, including erythropoiesis, glucose metabolism, angiogenesis, cell proliferation, and apoptosis. Despite this critical function, overexpression of HIFs has been observed in numerous cancers, leading to resistance to therapy and disease progression. In recent years, much effort has been poured into developing innovative cancer treatments that target the HIF pathway. Combining HIF inhibitors with current cancer therapies to increase anti-tumor activity and diminish treatment resistance is one strategy for combating therapeutic resistance. This review focuses on how HIF inhibitors could be applied in conjunction with current cancer treatments, including those now being evaluated in clinical trials, to usher in a new era of cancer therapy.

Effect of Dialysis Modalities on All-Cause Mortality and Cardiovascular Mortality in End-Stage Kidney Disease: A Taiwan Renal Registry Data System (TWRDS) 2005-2012 Study.

Introduction: End-stage kidney disease (ESKD) patients who need renal replacement therapy need to face a dialysis modality decision: the choice between hemodialysis (HD) and peritoneal dialysis (PD). Although the global differences in HD/PD penetration are affected by health-care policies, these two modalities may exert different effects on survival in patients with ESKD. Although Taiwan did not implicate PD as first policy, we still need to compare patients' outcomes using two modalities in a nation-wise database to determine future patients' care and health policies. Methods: We used the nationwide Taiwan Renal Registry Data System (TWRDS) database from 2005 to 2012 and included 52,900 patients (48,371 on HD and 4529 on PD) to determine all-cause and cardiovascular mortality among ESKD patients. Results: Age-matched survival probability from all-cause mortality was significantly lower in patients on PD than in those on HD (p < 0.05). The adjusted hazard ratios of 3-year and 5-year all-cause and cardiovascular mortality were significantly higher in PD compared with HD. The presence of comorbid conditions including myocardial infarction, coronary artery disease (CAD), diabetes mellitus (DM), hypoalbuminemia, hyperferritinemia and hypophosphatemia was related with significantly higher all-cause and CV mortality in PD patients. No significant difference was noted among younger patients <45 years of age regardless of DM and/or comorbid conditions. Conclusion: Although PD did not have the survival advantage compared to HD in all dialysis populations, PD was related with superior survival in younger non-DM patients, regardless of the presence of comorbidities. Similarly, for younger ESKD patients without the risk of CV disease, both PD and HD would be suitable dialysis modalities.

The Effect of Statin on Anemia in Patients with Chronic Kidney Disease and End-Stage Kidney Disease: A Systematic Review and Meta-Analysis.

Although erythropoietin-stimulating agents are effective in treating anemia in patients with end-stage kidney disease (ESKD) undergoing hemodialysis, some ESKD patients, especially those with inflammation, continue to suffer from anemia. Statin, an inhibitor of hydroxymethylglutaryl-CoA (HMG-CoA) reductase with lipid-lowering effects, may have a pleiotropic effect in reducing inflammation, and thus increase hemoglobin (Hb) level. We searched the PubMed, Embase, and Cochrane databases for relevant studies. The population of interest comprised advanced chronic kidney disease (CKD) patients and ESKD patients receiving hemodialysis with statin treatment. The included study designs were randomized control trial/cohort study/pre-post observational study, and outcomes of interest were Hb, erythropoietin resistance index (ERI) and ferritin. PRISMA 2020 guidelines were followed, and risk of bias (RoB) was assessed using the RoB 2.0 tool in randomized controlled trials, and the Newcastle-Ottawa scale (NOS) in cohort studies. We eventually included ten studies (5258 participants), comprising three randomized controlled trials and seven cohort studies. Overall, Hb increased by 0.84 g/dL (95% confidence interval [CI]: -0.02 to 1.70) in all groups using statins, including single-arm cohorts, and by 0.72 g/dL (95% CI: -0.02 to 1.46) in studies with placebo control. Hb levels were higher in the study group than in the control group, with a mean difference of 0.18 g/dL (95% CI: 0.04-0.32) at baseline and 1.0 g/dL (95% CI: 0.13-1.87) at the endpoint. Ferritin increased by 9.97 ng/mL (95% CI: -5.36 to 25.29) in the study group and decreased by 34.01 ng/mL (95% CI: -148.16 to 80.14) in the control group; ferritin fluctuation was higher in the control group. In conclusion, statin may improve renal anemia in ESKD patients receiving hemodialysis and regular erythropoietin-stimulating agents. Future studies with more rigorous methodology and larger sample size study should be performed to confirm this beneficial effect.