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.

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.

Bladder cancer is currently the most common malignant tumor of the urinary system. The traditional treatment methods for bladder cancer are mainly surgery, chemotherapy, radiotherapy, and targeted therapy; however, these treatment methods do not improve the clinical prognosis of patients with advanced or metastatic bladder cancer. Consequently, there is an urgent need to develop new treatment methods to improve the survival rate and quality-of-life of patients with bladder cancer. Over recent years, the rapid development of tumor immunotherapy has become a significant alternative to traditional treatment, and provides new hope to patients. This review aims to introduce neoantigens and their possible role in the treatment of bladder cancer, and to explore the current limitations of neoantigens for the treatment of bladder cancer.

Background: Telomere length is a potential prognostic biomarker in breast cancer, but its clinical utility remains uncertain due to inconsistent findings across the literature. This systematic review and meta-analysis aims to evaluate the association between telomere length and breast cancer survival outcomes, including overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), and recurrence-free survival (RFS). Methods: A systematic search of ten sources, including databases and publishers (JSTOR, Nature, ProQuest, PubMed, Sage Journals, ScienceDirect, Science, Scopus, Springer, and Wiley) was conducted to identify studies published up to December 31, 2023. Studies reporting associations between telomere length and survival outcomes in breast cancer patients were included. Hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CI) were extracted or calculated. Quality assessment was performed using the Newcastle-Ottawa Scale, and publication bias was evaluated using funnel plots, Egger’s, and Begg’s tests. Results: Nine studies involving 3,145 breast cancer patients were included. Shorter telomere length was significantly associated with increased recurrence risk (DFS/RFS) (pooled HR: 1.97; 95% CI: 1.04–3.74, P = 0.039), indicating a nearly twofold increase in risk. Trends toward worse OS (pooled HR: 1.60; 95% CI: 0.90–2.86, P = 0.110) and DSS (pooled HR: 1.09; 95% CI: 0.80–1.49, P = 0.565) were observed, but did not reach statistical significance. Additionally, shorter telomere length was significantly associated with premenopausal status (pooled OR: 1.34; 95% CI: 1.06–1.70, P = 0.01). Discussion: Shorter telomere length is associated with an increased risk of recurrence in breast cancer, highlighting its potential as a prognostic biomarker. However, further research is needed to standardize telomere length measurement methodologies and validate these findings across diverse populations and breast cancer subtypes.

Background: Preclinical animal studies have demonstrated that radiation treatment (RT) can induce effects beyond the anatomical site of irradiation. Non-targeted effects of RT (NTER) have been sporadically reported in clinical settings. However, with the advent of high-dose stereotactic radiation techniques (SRT) and immunotherapy (IT), renewed attention has been given to NTER. This systematic review aims to summarize current knowledge about NTER across various malignancies, with a focus on cases involving SRT. Methods: A systematic database search was performed, and records were screened following PRISMA guidelines. Only full-text original articles written in English and reporting clinical studies involving NTER after SRT were included. The results are categorized by cancer type, with separate general and critical analyses. Results: Sixty-three studies were reviewed, including 32 case reports/case series, 18 retrospective studies, and 13 prospective studies, predominantly published after 2018. NTER was most frequently observed in melanoma and lung cancer and commonly reported as the abscopal effect (AE), albeit with varying criteria. In most cases, IT with suboptimal response was ongoing at the time of SRT, and the median time to NTER onset was 3 months. Overall, NTER was documented in 297 patients: 34 from single cases and 263 from a pool of 1,212 evaluable patients (22%) across other studies. Prospective trials reported an NTER rate of 36%, rising to 56% in lung cancer. Discussion: In prospective clinical studies, the phenomenon of NTER following SRT has been observed in a significant proportion of patients. Nevertheless, the literature is limited, with small patient cohorts. Interest in NTER has grown, particularly in the context of IT. Standardization of definitions and reporting, along with the conduct of more clinical trials, is essential to better understand how NTER can be induced by SRT.

Multikinase inhibitors (MKIs) and highly selective tyrosine kinase inhibitors (HS-TKIs) positively impact the progression-free survival (PFS) of locally advanced and metastatic thyroid cancer cases. Moreover, disease-specific survival (DSS) and overall survival (OS) improvements were observed in some instances, suggesting a general benefit in disease control. In advanced and metastatic thyroid cancers, other conventional treatments are often ineffective when surgery cannot be performed due to the extension of the disease and/or the invasion of vital neck structures (such as the larynx, trachea, esophagus, recurrent laryngeal nerve, and carotid artery). In these cases, systemic treatments with MKIs and HS-TKIs have recently been evaluated for their potential to block tumor growth and reduce tumor size to make surgery possible or improve the control of metastatic disease. The study aimed to evaluate the performance of these systemic drugs in the neoadjuvant treatment of thyroid cancer patients, focusing on their efficacy according to the different histology.

Laryngeal cancer, a subtype of head and neck cancer, poses significant challenges due to its profound impact on essential functions such as speech and swallowing and poor survival rates in advanced stages. Traditional treatments—surgery, radiotherapy, and chemotherapy—are often associated with high morbidity and substantial recurrence rates, emphasizing the urgent need for novel therapeutic approaches. Immune checkpoint inhibitors (ICIs) have revolutionized oncology by countering tumor-induced immune evasion, restoring immune surveillance, and activating T-cell responses against cancer. This review examines the role of ICIs in laryngeal cancer management, with a focus on pembrolizumab and nivolumab (anti-PD-1 agents), which are clinically established, as well as investigational therapies such as dostarlimab (anti-PD-1), atezolizumab (anti-PD-L1), and ipilimumab (anti-CTLA-4). Pembrolizumab, in combination with platinum-based chemotherapy and 5-fluorouracil, is approved as a first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), based on evidence from the Keynote-048 trial. This pivotal trial demonstrated significant overall survival (OS) benefits over the cetuximab-based standard regimen. Similarly, nivolumab showed improved OS in the CheckMate-141 trial, supporting its approval as a second-line therapy for patients with platinum-refractory disease. ICIs have shown durable survival benefits and a more manageable toxicity profile compared to traditional chemotherapy. Immune-related adverse events are generally mild and controllable; however, in some cases, they can become severe and even life-threatening. Furthermore, ICIs are being investigated in combination with radiotherapy, as well as in neoadjuvant and adjuvant settings, where preliminary findings suggest these approaches may enhance efficacy, preserve organ function, and overcome resistance to conventional treatments. The integration of ICIs into multimodal treatment strategies holds promise for transforming the therapeutic landscape of advanced laryngeal cancer. This review synthesizes current evidence, highlights ongoing research, and explores strategies to enhance survival and quality of life for patients facing this challenging malignancy.

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.

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.

Background: Breast cancer is a leading cause of mortality in women. Hormone therapy plays a crucial role in treatment of hormone receptor-positive metastatic breast cancer. Elacestrant is a selective estrogen receptor degrader (SERD) that has shown promise in early-phase clinical trials. This post-hoc analysis systematically evaluates elacestrant’s effectiveness in hormone receptor-positive metastatic breast cancer patients, providing insights into its efficacy, safety, and potential advantages over existing treatments. Methods: We adhered to the PRISMA Statement 2020 guidelines and systematically searched the databases PubMed/MEDLINE, ClinicalTrials.gov, Web of Science, and Embase. We conducted the post-hoc analysis using R software (V 4.3.3), applying the inverse variance method and the DerSimonian-Laird estimator to pool effect estimates with a random-effects model. We assessed heterogeneity using the Cochran’s Q test and the I2 statistic. Results: Our post-hoc analysis encompassed 3 clinical trials and a total of 835 participants. The mean age of all 835 participants across the three trials was 59.5 years (95% CI: 58.7–60.3). The pooled progression-free survival (PFS)—was estimated at 4.38 (95% CI: –7.58–16.35, P = 0.47), and the pooled objective response rate (ORR) was 7% (95% CI: 2–18%, P = 0.04), with significant heterogeneity observed among the studies. Discussion: Elacestrant shows promise for improving outcomes in hormone receptor-positive metastatic breast cancer, but further research is needed to confirm its effectiveness. Future studies should include larger sample sizes, comprehensive phase II and III trials, and investigation of elacestrant in combination with other drugs or in preoperative settings.