Exploration of targeted anti-tumor therapy最新文献

Aim: The interaction of concomitant benzodiazepine (BZD) exposure during immune checkpoint blockade has not been comprehensively investigated to date. This research aimed to determine the influence of BZD intake on the survival outcomes of patients with metastatic non-small-cell lung cancer (NSCLC) receiving pembrolizumab-based therapies.

Methods: We included consecutive patients with advanced NSCLC who were given frontline pembrolizumab, whether as exclusive therapy or combined with platinum-based chemotherapy. The classification of BZD relied on the molecular composition, distinguishing between N-substituted and N-unsubstituted compounds.

Results: During the time frame from April 2018 to May 2023, we enrolled 258 patients, 156 (60.5%) and 102 (39.5%) of whom received pembrolizumab alone or the combination regimen, respectively. We identified 108 (41.8%) exposed patients (BZD cohort) in comparison to all others (no-BZD cohort). After applying propensity-score matching, 108 cases were relevant for each cohort. After a median follow-up of 16.3 [95% confidence interval (CI) 13.1-19.7] months, univariate analysis revealed no significant differences in terms of progression-free survival (PFS) or overall survival (OS) between BZD cohorts. However, patients exposed to N-substituted compounds had significantly longer PFS and OS than those who did not take BZD. Conversely, patients exposed to N-unsubstituted compounds experienced significantly shortened OS. Multivariate testing showed that taking unspecified BZD had no impact on PFS or OS, while N-substituted BZD exposure correlated independently with longer PFS [hazard ratio (HR) 0.52 (95% CI 0.34-0.79); P = 0.002] and OS [HR 0.58 (95% CI 0.38-0.88); P < 0.001]. In contrast, N-unsubstituted BZD intake had worsening effects on OS [HR 1.92 (95% CI 1.20-3.06); P = 0.006].

Conclusions: BZD exposure may impact the efficacy of immune checkpoint inhibitors in patients with advanced NSCLC. The specific composition may influence the choice among different compounds.

The discovery of oncogenes and tumor suppressor genes led to a better understanding of tumorigenesis, and prompted the development of molecularly targeted therapy. Over the past 30 years, many new drugs, which are primarily aimed at activated oncogenic proteins in signal transduction pathways involved in cell proliferation and survival, have been introduced in the clinic. Despite its rational design, the overall efficacy of targeted therapy has been modest. Recently, the noncoding RNAs (ncRNAs) have emerged as key regulators of important cellular processes in addition to the known regulatory proteins. It now appears that dual epigenetic regulatory systems exist in higher eukaryotic cells: a ncRNA network that governs essential cell functions, like cell fate decision and maintenance of homeostasis, and a protein-based system that presides over core physiological processes, like cell division and genomic maintenance. Modifications of the ncRNA network due to altered ncRNAs can cause the cell to shift towards to neoplastic phenotype; this is cancer initiation. Mutations in the well-known cancer driver genes provide the incipient cancer cell with a selective growth advantage and fuel its consequent clonal expansion. Because of the crucial role of the altered ncRNAs in tumorigenesis, targeting them may be a reasonable therapeutic strategy.

Cancer is the greatest cause of mortality worldwide. Various drug classes treat various cancers. Nanoformulations made from natural sources are being studied for treating several diseases, including cancer. Surgery, chemotherapy, immunotherapy, and radiation have mostly failed to treat cancer. These drugs may damage quickly dividing healthy tissues, structural anomalies, bodily toxicity, long-term side effects, tumor cell drug resistance, and psychiatric disturbances. Researchers are developing nanoscale medicines using natural medications like Malva sylvestris and Curcumin to lower concentrations and improve target specificity. Nanoparticles' small size and unique properties make them beneficial. They encapsulate medicinal ingredients, improving solubility, medication release, cellular absorption, and delivery. Nanoparticles may better identify and bind to cancer cells when functionalized with ligands. Natural chemicals and nanotechnology may improve medication availability, distribution, and targeting to cancer cells, making cancer treatments more effective and safe. Nanomedicine, which employs nanoparticles to treat cancer and malignant cells, has grown rapidly because nanodrugs are more effective and have fewer side effects than current commercial cancer drugs. Nanotechnology-based natural chemicals and pharmaceutical delivery methods for cancer therapy are covered in this review article. The paper discusses nanoparticle pros and cons and natural chemicals' cancer-fighting appeal.

Aim: Breast cancer (BC), a disease in which abnormal breast cells grow out of control and form tumors, is a prevalent life-threatening disease worldwide. Oxidative stress has been implicated in the development and progression of various cancers, including BC. Assessing lipid peroxidation and overall antioxidant status in BC offers valuable information on disease progression, patient prognosis, and the effectiveness of therapeutic options.

Methods: A total of 150 women were categorized into three groups: normal, benign mass, and BC. Participants were selected and evaluated at the cancer clinic; fasting blood samples were collected, and total antioxidant capacity (TAC), oxidized low-density lipoprotein (Ox-LDL), cancer antigen (CA) 15-3, and carcinoembryonic antigen (CEA) were measured. Subsequently, statistical analysis was performed to compare the levels of these parameters in different groups and examine the analytical performance of TAC and Ox-LDL in BC.

Results: In patients with malignancy, the serum level of TAC was significantly decreased compared with the benign group (8.3 U/mL and 16.04 U/mL, respectively) (P < 0.001). Healthy controls exhibited higher levels of TAC (43.4 U/mL). The levels of Ox-LDL in BC were significantly increased in both malignant and benign groups (3,831 pg/mL and 1,234 pg/mL, respectively) compared with normal controls (682 pg/mL) (P < 0.001). CEA and CA15-3 were drastically increased in the BC groups compared with the control group. A significant area under the curve was observed in the receiver operating characteristic (ROC) curve analysis for TAC (0.975, P < 0.001) and Ox-LDL (0.986, P < 0.001).

Conclusions: This study revealed that patients with BC had lower TAC and higher Ox-LDL serum levels, indicating elevated oxidative stress. These levels may serve as promising monitoring parameters in BC.