Predictive value of frailty assessment tools in patients undergoingsurgery for gastrointestinal cancer: An observational cohort study

BACKGROUND Few studies have simultaneously compared the predictive value of various frailty assessment tools for outcome measures in patients undergoing gastrointestinal cancer surgery.Therefore,it is difficult to determine which assessment tool is most relevant to the prognosis of this population.AIM To investigate the predictive value of three frailty assessment tools for patient prognosis in patients undergoing gastrointestinal cancer surgery.METHODS This single-centre,observational,prospective cohort study was conducted at the Affiliated Lianyungang Hospital of Xuzhou Medical University from August 2021 to July 2022.A total of 229 patients aged≥18 years who underwent surgery for gastrointestinal cancer were included in this study.We collected baseline data on the participants and administered three scales to assess frailty:The comprehen-sive geriatric assessment(CGA),Fried phenotype and FRAIL scale.The outcome measures were the postoperative severe complications and increased hospital RESULTS The prevalence of frailty when assessed with the CGA was 65.9%,47.6%when assessed with the Fried phenotype,and 34.9%when assessed with the FRAIL scale.Using the CGA as a reference,kappa coefficients were 0.398 for the Fried phenotype and 0.291 for the FRAIL scale(both P<0.001).Postoperative severe complications and increased hospital costs were observed in 29(12.7%)and 57(24.9%)patients,respectively.Multivariate logistic analysis confirmed that the CGA was independently associated with increased hospital costs(odds ratio=2.298,95%confidence interval:1.044-5.057;P=0.039).None of the frailty assessment tools were associated with postoperative severe complications.CONCLUSION The CGA was an independent predictor of increased hospital costs in patients undergoing surgery for gastro-intestinal cancer.

Targeting cancer stem cells in drug discovery: Current state and future perspectives

In recent decades,cancer stem cells(CSCs)have been increasingly identified in many malignancies.CSC-related signaling pathways and their functions provide new strategies for treating cancer.The aberrant activation of related signaling pathways(e.g.,Wnt,Notch,and Hedgehog pathways)has been linked to multiple types of malignant tumors,which makes these pathways attractive targets for cancer therapy.CSCs display many characteristic features,such as self-renewal,differentiation,high tumorigenicity,and drug resistance.Therefore,there is an urgent need to develop new therapeutic strategies to target these pathways to control stem cell replication,survival,and differentiation.Notable crosstalk occurs among different signaling pathways and potentially leads to compensatory escape.Therefore,multitarget inhibitors will be one of the main methods to overcome the drug resistance of CSCs.Many small molecule inhibitors of components of signaling pathways in CSCs have entered clinical trials,and some inhibitors,such as vismodegib,sonidegib,and glasdegib,have been approved.Tumor cells are susceptible to sonidegib and vismodegib resistance due to mutations in the Smo protein.The signal transducers and activators of transcription 3(STAT3)inhibitor BBI608 is being evaluated in a phase III trial for a variety of cancers.Structural derivatives of BBI608 are the main focus of STAT3 inhibitor development,which is another strategy for CSC therapy.In addition to the potential pharmacological inhibitors targeting CSCrelated signaling pathways,other methods of targeting CSCs are available,such as nano-drug delivery systems,mitochondrion targeting,autophagy,hyperthermia,immunotherapy,and CSC microenvironment targeting.In addition,we summarize the latest advances in the clinical development of agents targeting CSC-related signaling pathways and other methods of targeting CSCs.