Risk Factors of Chemotherapy-Induced Thrombocytopenia After Oxaliplatin-Containing Chemotherapy for Gastrointestinal Malignancies.

PURPOSE: Thrombocytopenia is among the most common chemotherapy-related hematologic toxicities. We aim to determine the predictors of oxaliplatin chemotherapy-induced thrombocytopenia in patients with gastrointestinal tumors to guide the clinic. METHODS: Clinical data of 750 patients with a malignant gastrointestinal tumor were included as the primary cohort. Basic clinical data, serological indices, and anthropometric indices of these patients were collected. According to the presence or absence of CIT, univariate analysis was performed to identify significant factors for multivariate analysis. In R language software, nomogram was constructed based on the results of multi-factor analysis, and the calibration curve and ROC curve were drawn. RESULTS: Univariate analysis identified 17 factors as closely related to CIT occurrence, namely age, lymph node metastasis (N) stage, metastasis (M) stage, lung metastasis, other site metastasis, chemotherapy regimen, course of treatment, total dose of oxaliplatin, AST, albumin, neutrophils, monocytes, baseline platelets, transferrin, natural killer (NK) cell, phase angle, and SMI (P < 0.10). The binary logistic multivariate regression analysis revealed five independent risk factors for developing CIT (P < 0.05), including the M stage, total dose of oxaliplatin, albumin, baseline thrombocyte count, and NK cell. Based on the results of multivariate logistic regression analysis, R software was used to establish a nomogram model. The calibration curve shows that the combined predictor has good consistency. The area under the ROC curve was 0.877 and the best cut-off value was 0.3579613 (sensitivity, 78.9%; specificity, 81.8%), which showed the better prediction efficiency. CONCLUSION: The total dose of oxaliplatin, M stage, albumin, baseline platelet count, and NK cell was independent risk factors for CIT. The sequentially constructed histogram model had a good predictive effect on the risk of thrombocytopenia caused by oxaliplatin chemotherapy in patients with gastrointestinal malignancies.

FBXW7 and human tumors: mechanisms of drug resistance and potential therapeutic strategies.

Drug therapy, including chemotherapy, targeted therapy, immunotherapy, and endocrine therapy, stands as the foremost therapeutic approach for contemporary human malignancies. However, increasing drug resistance during antineoplastic therapy has become a substantial barrier to favorable outcomes in cancer patients. To enhance the effectiveness of different cancer therapies, an in-depth understanding of the unique mechanisms underlying tumor drug resistance and the subsequent surmounting of antitumor drug resistance is required. Recently, F-box and WD Repeat Domain-containing-7 (FBXW7), a recognized tumor suppressor, has been found to be highly associated with tumor therapy resistance. This review provides a comprehensive summary of the underlying mechanisms through which FBXW7 facilitates the development of drug resistance in cancer. Additionally, this review elucidates the role of FBXW7 in therapeutic resistance of various types of human tumors. The strategies and challenges implicated in overcoming tumor therapy resistance by targeting FBXW7 are also discussed.