Background: The CD133 antigen is a marker of radio- and chemo-resistant stem cell populations in glioblastoma (GBM). The O⁶-methylguanine DNA methyltransferase (MGMT) enzyme is related with temozolomide (TMZ) resistance. Our propose is to analyze the prognostic significance of the CD133 antigen and promoter methylation and protein expression of MGMT in a homogenous group of GBM patients uniformly treated with radiotherapy and TMZ. The possible connection between these GBM markers was also investigated.Methods: Seventy-eight patients with GBM treated with radiotherapy combined with concomitant and adjuvant TMZ were analyzed for MGMT and CD133. MGMT gene promoter methylation was determined by methylation-specific polymerase chain reaction after bisulfite treatment. MGMT and CD133 expression was assessed immunohistochemically using an automatic quantification system. Overall and progression-free survival was calculated according to the Kaplan–Meier method.Results: The MGMT gene promoter was found to be methylated in 34 patients (44.7%) and unmethylated in 42 patients (55.3%). A significant correlation was observed between MGMT promoter methylation and patients’ survival. Among the unmethylated tumors, 52.4% showed low expression of MGMT and 47.6% showed high-expression. Among methylated tumors, 58.8% showed low-expression of MGMT and 41.2% showed high-expression. No correlation was found between MGMT promoter methylation and MGMT expression, or MGMT expression and survival. In contrast with recent results, CD133 expression was not a predictive marker in GBM patients. Analyses of possible correlation between CD133 expression and MGMT protein expression or MGMT promoter methylation were negative.Conclusions: Our results support the hypothesis that MGMT promoter methylation status but not MGMT expression may be a predictive biomarker in the treatment of patients with GBM. In addition, CD133 should not be used for prognostic evaluation of these patients. Future studies will be necessary to determine its clinical utility.

Nasopharyngeal carcinoma (NPC) is distinct from other cancers of the head and neck in biology, epidemiology, histology, natural history, and response to treatment. Radiation therapy is an essential component of curative-intent of non-disseminated disease and the association of chemotherapy improves the rates of survival. In the case of metastatic disease stages, treatment requires platinum/gemcitabine-based chemotherapy and patients may achieve a long survival time.

Carboplatin-paclitaxel is a reference regimen in the treatment of locally advanced or disseminated non-small cell lung cancer (NSCLC). This paper discusses the multidrug resistance developed with this drug combination, which is one of the major obstacles to successful treatment. In order to understand and overcome the drug resistance pattern of NSCLC after carboplatin plus paclitaxel exposure, levels of mRNA expression of multidrug resistance 1 (MDR1) and multidrug resistance-associated protein 3 (MRP3) were investigated in primary NSCLC cell lines (A-549 and A-427) and a metastasis-derived NSCLC cell line (NODO). Our results showed that exposure of the three NSCLC lines to plasma concentrations of paclitaxel (5 μM) produced an increase in MDR1 expression, while MRP3 showed no alteration in expression. By contrast, the same cells exposed to carboplatin plasma concentrations (30 μM) showed overexpression of MRP3. In these cells, MDR1 showed no expression changes. Interestingly, the combination of both paclitaxel and carboplatin caused increased expression of the MDR1 drug resistance gene rather than the individual treatments. These results suggest that carboplatin and paclitaxel may induce drug resistance mediated by MDR1 and MRP3, which may be enhanced by the simultaneous use of both drugs.

Purpose: Strategies for the treatment of liver metastases from colon cancer (lmCRC) are constantly evolving. Radioembolization with yttrium 90 (Y-90 TARE) has made significant advancements in treating liver tumors and is now considered a potential option allowing for future resection. This study reviewed the scientific evidence and developed recommendations for using Y-90 TARE as a treatment strategy for patients with unresectable lmCRC. Methods: A multidisciplinary scientific committee, consisting of experts in medical oncology, hepatobiliary surgery, radiology, and nuclear medicine, all with extensive experience in treating patients with ImCRC with Y-90 TARE, led this project. The committee established the criteria for conducting a comprehensive literature review on Y-90 TARE in the treatment of lmCRC. The data extraction process involved addressing initial preliminary inquiries, which were consolidated into a final set of questions. Results: This review offers recommendations for treating patients with lmCRC using Y-90 TARE, addressing four areas covering ten common questions: 1) General issues (multidisciplinary tumor committee, indications for treatment, contraindications); 2) Previous process (predictive biomarkers for patient selection, preintervention tests, published evidence); 3) Procedure (standard procedure); and 4) Post-intervention follow-up (potential toxicity and its management, parameters for evaluation, quality of life). Conclusions: Based on the insights of the multidisciplinary committee, this document offers a comprehensive overview of the technical aspects involved in the management of Y-90 TARE. It synthesizes recommendations for applying Y-90 TARE across various phases of the treatment process.

Background/Objectives: Irinotecan is used in monotherapy or combined with other drugs for treating different cancer streams. SN-38, the active metabolite of irinotecan, is 70% inactivated by the uridine diphosphate (UDP) glucuronosyltransferase family 1 member A1 (UGT1A1) enzyme. The UGT1A1*6 (rs4148323) and *28 (rs3064744) alleles in the gene encoding the enzyme lead to decreased enzyme expression and increased severe irinotecan toxicity. Carrying one or two copies of these alleles results in a UGT1A1 intermediate or poor metabolizer status (IM, PM). The Food and Drug Administration (FDA)-approved drug labels and European Medicines Agency (EMA) European Public Assessment Report (EPAR) for irinotecan recommend dose adjustments based on UGT1A1 genotypes, but only for UGT1A1 PM patients. However, available pharmacogenetic (PGx) dosing guidelines for the UGT1A1–irinotecan interaction lack a consensus about considered genetic variants, genotype-translated phenotypes, and therapeutic recommendations. We aimed to describe evidence regarding the impact of the UGT1A1 genotype in irinotecan toxicity to inform irinotecan-dosing recommendations based on possible UGT1A1 genotypes. Methods: A systematic review was performed to find all the Phase I clinical trials looking for the maximum tolerated dose (MTD) or dose-limiting toxicities (DLTs) of irinotecan depending on the UGT1A1 genotype. Results: Toxicity-related events and the MTD of irinotecan differ among UGT1A1 normal metabolizers (NM), IM, and PM patients considering the UGT1A1*28 and/or *6 variants. Conclusions: Dose adjustments might also be recommended for UGT1A1 IM patients (*1/*28 or *1/*6 genotypes), with a 15% dose reduction considered.

Trifluridine/tipiracil is currently approved for metastatic colorectal cancer (mCRC) refractory to available therapies. However, there is no consensus on factors that predict treatment outcomes in daily practice. We assessed the early clinical experience with trifluridine/tipiracil in Spain and potential survival markers. This was a retrospective cohort study of mCRC patients who participated in the trifluridine/tipiracil early clinical experience programme in Spain. The primary outcome was overall survival (OS). Associations between OS and patient characteristics were assessed using multivariate Cox regression analyses. A total of 379 patients were included in the study. Trifluridine/tipiracil was administered for a median of 3.0 cycles and discontinued mainly due to disease progression (79.2%). The median OS was 7.9 months, with a 12-month OS rate of 30.5%. Cox analyses revealed that the following variables independently enhanced OS: ≤2 metastatic sites, no liver metastasis, alkaline phosphatase < 300 IU, trifluridine/tipiracil dose reductions, and neutrophil/lymphocyte ratio < 5. Grade ≥ 3 toxicities were reported in 141 (37.2%) patients, including mainly afebrile neutropaenia (23.2%), anaemia (12.1%), and thrombocytopaenia (5.3%). This study supports the real-life efficacy and safety of trifluridine/tipiracil for refractory mCRC and identifies tumour burden, liver metastasis, alkaline phosphatase, dose reductions, and neutrophil/lymphocyte ratio as survival markers.