Pharmacogenetics plays an increasingly important role in oncology by supporting individualized therapeutic strategies based on patient genetic profiles. ClinicalTrials.gov provides a valuable platform for evaluating global trends in pharmacogenetic anticancer clinical trials. This systematic review aimed to evaluate pharmacogenetic-focused anticancer clinical trials registered on ClinicalTrials.gov and summarize trends in study design, cancer types, targeted biomarkers, therapeutic interventions, and geographic distribution.

Microsatellite instability (MSI) is a key biomarker for immunotherapy in gastric cancer (GC), but preoperative non-invasive prediction remains challenging. Radiomics is promising; however, a systematic evaluation of its diagnostic performance with explicit consideration of overfitting and model comparison is lacking.

Chronic myeloid leukemia (CML) with megakaryoblastic blast crisis (MKBC) as the initial manifestation is extremely rare, accounting for less than 3% of all CML cases. Philadelphia chromosome-positive acute myeloid leukemia, FAB M7 subtype (Ph+ AML-M7), is also known as Philadelphia chromosome-positive acute megakaryoblastic leukemia (Ph+ AMKL), representing a distinct and prognostically unfavorable category of AML. Morphologically and immunophenotypically, these two entities are nearly identical, posing significant diagnostic challenges. We describe a novel case of Ph+ leukemia with MKBC differentiation that appears most consistent with CML in blast phase (BP). Following treatment with a tyrosine kinase inhibitor (TKI) combined with induction and consolidation chemotherapy, the patient achieved complete remission (CR). Although hematopoietic stem cell transplantation (HSCT) was declined due to economic constraints, the patient has maintained deep molecular remission(MR5, BCR::ABL1IS ≤ 0.001%)for 35 months to date. Through a systematic review of existing literature, this article elucidates key discriminative features between the two conditions and proposes a practical diagnostic and therapeutic framework to guide clinical decision-making.

The primary aim of this review is to summarize current evidence from clinical and pre-clinical studies on endogenous molecular biomarkers associated with radiosensitivity and radioresistance in cervical cancer, including patients treated with photon-based radiotherapy, cervical cancer cell lines, and xenograft models, and to evaluate the association of these biomarkers with radiotherapy response, residual disease, recurrence and survival, and experimental measures of radiosensitivity. A systematic literature review was conducted for studies published over the last 10 years that evaluated associations between genomic, epigenetic, or protein biomarkers and radiotherapy response or survival outcomes in cervical cancer. Eligible studies included in the current analysis summarize clinical, translational, and pre-clinical studies in correlation with photon-based radiotherapy. Research focusing exclusively on non-coding RNAs, exogenous radiosensitizers, or non-photon modalities was excluded. In total, 112 studies were identified, and 46 of them met the inclusion criteria. The identified biomarkers clustered into several key biological processes: DNA damage response and cell cycle regulation, cancer stemness, hypoxia and microenvironment, epigenetic and transcriptional regulation, and signaling pathways, including exosome-mediated communication. Most markers were linked to radioresistance and adverse outcomes, whereas a smaller subset was associated with increased radiosensitivity. A limited group of biomarkers was linked to clinical outcomes such as local control, residual disease, or survival, and emerging multi-marker protein signatures suggested that combinatorial approaches may outperform single-marker strategies. Radiosensitivity in cervical cancer is regulated by a network of biological pathways. Validated, integrated biomarker panels that capture DNA repair proficiency, stemness, hypoxia adaptation, and key signaling pathways are needed to improve risk stratification and enable biomarker-guided radiosensitization.

Non-small-cell lung cancer (NSCLC) is one of the most frequent cancer types and is responsible for the majority of cancer-related deaths worldwide. For this reason, initial diagnosis, prognosis, and targeted therapy of NSCLC represent very attractive areas of study. Aptamers are single-stranded nucleic acids (RNA or DNA) generated through Systematic Evolution of Ligands by Exponential Enrichment (SELEX); they are able to bind to a molecular target with high affinity and specificity. Thanks to their intrinsic nucleic acid properties, they can be easily modified and optimized to enhance target binding and their half-life; moreover, they exhibit no immunogenicity and toxicity. Due to this, many aptamers have just been selected against NSCLC biomarkers and provide specific imaging agents to improve the diagnosis of this type of cancer. However, despite the promising results in preclinical studies, the application of aptamers in NSCLC diagnosis is still in its early stages, mainly due to the limited literature in the research world, the dominance of antibodies in the pharmaceutical market and the challenge of target identification. Consequently, this appears to be a temporary issue, and aptamers could see increasing application in the future; thus, we performed a review aimed at summarizing current knowledge on the new promising DNA and RNA aptamer-based molecules for NSCLC diagnosis. All studies from 2000 were included and investigated. Our findings showed that several DNA and RNA aptamers are promising diagnostic tools for NSCLC management.

The chances of oral squamous cell carcinoma (OSCC) being diagnosed at an early stage are very low, and this leads to a poor prognosis. The presence of circulating miRNAs (miRNAs) in blood or saliva is now a potential non-invasive diagnostic biomarker, although the diagnostic accuracy of the studies reported remains vastly different due to differences in biofluids, miRNA panels, disease spectrum, and platforms.

Ropeginterferon alfa-2b, a novel monopegylated interferon with improved pharmacokinetics, has emerged as a promising cytoreductive agent for managing polycythemia vera (PV). Despite increasing adoption, evidence synthesis of its efficacy and safety compared to standard care remains limited. The manuscript aimed to evaluate the efficacy of ropeginterferon alfa-2b in comparison to standard treatment options, including hydroxyurea and phlebotomy, in achieving complete hematologic response, partial molecular response (PMR), and reducing JAK2V617F allele burden in patients with PV.

Trophoblast cell surface antigen 2 (Trop-2) is a targetable transmembrane glycoprotein commonly overexpressed in breast cancer (BC). This study combines a systematic review and meta-analysis with a retrospective analysis of an independent early BC patient cohort, aiming to investigate the expression patterns of Trop-2 and their clinical significance in BC.

This systematic review with functional meta-synthesis and exploratory meta-analysis evaluated the clinical utility of molecular testing in ameloblastoma, focusing on diagnostic, genotype-phenotype, prognostic, liquid-biopsy, and precision-therapy implications.

KRAS mutations are common in colorectal cancer, but the impact of KRAS mutation subtypes on treatment response remains poorly understood. This research aimed to investigate whether different KRAS mutations influence pathological complete response (pCR) rates after neoadjuvant chemoradiotherapy in locally advanced rectal cancer (LARC).

Background and objectives Despite substantial research on immunotherapy, its efficacy and safety in treating advanced non-small cell lung cancer (NSCLC) without identifiable driver mutations remain unclear. The objective of this review was to examine the efficacy and safety of immunotherapy, used as monotherapy or alongside chemotherapy, vs. chemotherapy alone in patients with advanced driver mutation-negative NSCLC. Methods A comprehensive literature search of PubMed, Embase, Scopus, and CENTRAL databases was conducted until December 2024. The protocol was registered in PROSPERO (CRD42024585050). Randomised controlled trials (RCTs) evaluating the efficacy and safety of immunotherapy, either as monotherapy or in combination with chemotherapy, compared with chemotherapy alone, were included. A random-effects meta-analysis was performed. Risk of bias was assessed using the Cochrane RoB 2 tool, and the certainty of evidence was evaluated using the GRADE framework. Results Twenty-three RCTs (n=14605 participants) were included. Immunotherapy (± chemotherapy) significantly improved overall survival [22 RCTs; 14,375 participants, hazard ratio (HR): 0.77; 95% Confidence interval (CI): 0.72-0.83] and progression-free survival (22 RCTs; 14,003 participants, HR: 0.67; 95% CI: 0.58-0.76) compared with chemotherapy alone. The objective response rate was also higher with immunotherapy (23 RCTs; 12,967 participants, RR 1.38, 95% CI: 1.24-1.54). No statistically significant differences were observed between the groups in terms of overall adverse event rates. Interpretation and conclusions Immunotherapy, whether administered alone or in combination with chemotherapy, provides significant survival benefits in patients with advanced driver mutation-negative NSCLC.

Androgen receptor splice variant 7 (AR-V7) is associated with resistance to androgen receptor-targeting therapies in prostate cancer, but its prevalence and clinical relevance in non-prostatic cancers remain incompletely characterized. A systematic review was conducted in accordance with PRISMA guidelines. Thirty-four studies, including 4855 clinical cases and 60 cell lines, were included. Overall, AR-V7 positivity was reported in 948/4855 clinical cases (19.5%); however, this represents a descriptive estimate across heterogeneous tumor types, study designs, and detection methods. Breast cancer accounted for 4057 of 4855 clinical cases (83.6%) and 815 of 948 AR-V7-positive cases (86.0%), with a within-cancer prevalence of 20.1%. However, after excluding the TCGA cohort in which AR-V7 was inferred through splice-junction analysis, the prevalence of AR-V7-positive breast cancer decreased to 9%. Higher tumor-specific proportions were observed in salivary duct carcinoma (55.2%), hepatocellular carcinoma (57.1%), and non-muscle-invasive bladder cancer (82.6%), but these estimates were based on smaller cohorts and should be interpreted cautiously. AR-V7 was present in several treatment-naive non-prostatic cancers, suggesting that it may represent a preexisting molecular feature in selected contexts. Current evidence suggests that AR-V7 warrants further investigation as a candidate biomarker. Standardized detection methods and prospective studies are needed before its clinical utility can be established.

This study aimed to evaluate the first-line treatment patterns and prognostic factors associated with survival in patients with driver gene-negative non-small cell lung cancer (NSCLC) and liver metastases, in order to identify the optimal treatment strategy.

Ectopic hepatocellular carcinoma (EHCC) is an exceedingly rare malignancy characterized by its occurrence outside the liver without a detectable intrahepatic primary tumor. Owing to its rarity and the absence of standardized management guidelines, the diagnosis and treatment of EHCC pose significant challenges.

Colorectal cancer (CRC) continues to be a significant global health issue. Thymoquinone (TQ), a bioactive component of Nigella sativa, has shown anticancer capabilities by inducing apoptosis. This systematic review and meta-analysis aim to assess the impact of TQ on the levels of pro-apoptotic (BAX, CASP3) and anti-apoptotic (BCL2) markers in colorectal cancer cells.

MicroRNAs are important regulators of melanoma progression; however, their relationship with cellular senescence remains poorly understood. To address this gap, a systematic review was conducted following PRISMA 2020 guidelines and prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD420251155760. A comprehensive search of PubMed, Scopus, Embase, and Dimensions identified studies evaluating melanoma-associated microRNAs and their effects on cell cycle regulation. Risk of bias was assessed using the SYRCLE tool and an adapted version of ToxRTool, with the included studies classified as having low, moderate, or high risk of bias. Fifteen studies met the eligibility criteria. Most studies reported that microRNA modulation reduced melanoma proliferation through cell cycle arrest; however, only two directly assessed senescence-associated markers. Of the fifteen identified microRNAs, seven had predicted targets and were included in the bioinformatic analysis. Integration of these predictions with genes downregulated in high-risk melanoma and underexpressed during cellular senescence identified 158 shared genes. Subsequent analysis identified predicted targets within this gene set only for hsa-miR-195-5p, and hsa-miR-425-5p, highlighting RNF138, and SYNCRIP as candidate regulatory genes. Collectively, these findings suggest a potential link between microRNA-mediated regulation and senescence-associated pathways during melanoma progression.

Circadian rhythms synchronize physiological processes with the light-dark cycle and regulate biological functions relevant to cancer, including cell-cycle control, metabolism, DNA repair, immunity, and tissue homeostasis. Growing evidence indicates that disruption of these temporal mechanisms contributes to tumor initiation, progression, metastasis, and treatment response. In colorectal cancer (CRC), circadian clock dysregulation has emerged as an important component of tumor biology. A systematic search identified 1338 records, of which 43 studies met the eligibility criteria (20 human, 19 experimental, and 4 chronotherapy studies). Across the included studies, statistically significant associations were consistently reported between dysregulation of clock genes such as PER1, PER3, CLOCK, BMAL1, CRY1, TIMELESS, and ARNTL2 and alterations in proliferation, metabolism, epithelial plasticity, immune regulation, metastatic potential, and treatment responsiveness. Experimental evidence also supported interactions with Wnt signaling, ferroptosis, oxidative-stress adaptation, epithelial-mesenchymal remodeling, and a proposed clock-microbiota-immune axis. Overall, the available evidence indicates that circadian dysregulation represents a systems-level disturbance that gives rise to a multidimensional biological condition, here referred to as the Tumor Temporal State, integrating the metabolic, immune, invasive, and therapeutic dimensions of colorectal cancer biology.

Salivary gland cancers (SGCs) are rare and heterogeneous tumours, making the identification of reliable prognostic biomarkers challenging. MicroRNAs (miRNAs) regulate post-transcriptional gene expression and may play important roles in tumour progression and treatment response. This systematic review aims to identify and summarize the current evidence on miRNA dysregulation in SGCs, with a particular focus on their prognostic relevance and therapeutic potential. A systematic search of PubMed/MEDLINE, Embase, Web of Science, and the Cochrane Library was conducted up to 3 December 2025, following PRISMA guidelines and a pre-registered protocol (CRD420251231827). Observational cohort and cross-sectional studies reporting microRNA dysregulation in human salivary gland tissues with prognostic assessment were included. Risk of bias was assessed using the Quality in Prognosis Studies (QUIPS) tool. Due to considerable heterogeneity, a narrative synthesis was conducted. Twenty studies published between 2013 and 2025 that fulfilled the search criteria were further analyzed. Based on the currently available evidence, dysregulation of miRNAs associated with prognosis has been identified only in adenoid cystic carcinoma (AdCC) and mucoepidermoid carcinoma (MEC). Most studies originated from Asia and used qRT-PCR for miRNA assessment. Most researchers focused on the evaluation of selected candidate miRNAs, rather than conducting comprehensive miRNA profiling approaches in relation to prognosis. Several distinct dysregulated miRNAs were identified across the studies. Among them, miR-9, miR-21, miR-24 miR-29, miR-34c-5p, miR-125a-5p, miR-143, miR-145 and miR-205 were reported in more than one study and linked to clinicopathological advancement and a more aggressive disease course, thus leading to a poorer outcome. MiRNAs appear to represent promising prognostic biomarkers, either as independent predictors or in combination with established clinicopathological features. However, current evidence remains limited to selected histological subtypes and relatively small patient cohorts. Further well-designed studies with long-term follow-up are required. Moreover, comprehensive miRNA profiling with prognosis assessment is necessary before specific miRNAs could be reliably established as biomarkers and utilized in daily clinical practice.

Background/Objectives: Outcomes after CD19-directed chimeric antigen receptor (CAR) T-cell therapy for relapsed or refractory (R/R) aggressive large B-cell lymphoma (aLBCL) remain heterogeneous. Tumor genomic biomarkers, such as TP53 alteration, MYC/BCL2/BCL6 rearrangement-defined double-hit or triple-hit lymphoma (DHL/THL), cell of origin (COO), and complex karyotype, are established or candidate prognostic factors in conventionally treated lymphoma, but their relevance after CAR T-cell therapy is uncertain. We conducted a systematic review with exploratory meta-analysis of biomarker-stratified outcomes after CD19 CAR T-cell therapy in aLBCL. Methods: We searched MEDLINE, Embase, and Web of Science/BIOSIS (April 2026), with targeted PubMed citation lookup during full-text retrieval (PROSPERO CRD420261350514). Eligible studies enrolled adults with R/R disease treated with protocol-eligible CD19 CAR T-cell therapy and reported prespecified tumor genomic biomarkers with stratified outcomes. Random-effects models, using restricted maximum-likelihood estimation with Hartung-Knapp-Sidik-Jonkman (HKSJ) adjustment, were fitted when at least three comparable, non-overlapping studies provided extractable data. Results: After duplicate removal, 182 records were screened, 37 were assessed for eligibility, and 26 studies were included in the qualitative synthesis; 10 contributed to 4 pooled analyses. DHL/THL-positive disease was associated with worse unadjusted overall survival (OS) (hazard ratio [HR] 1.52; 95% confidence interval [CI], 1.21-1.89; 95% prediction interval (PI), 0.56-4.08), and non-Germinal center B-cell-like (GCB)/ABC COO with worse adjusted progression-free survival (PFS) (HR 1.44; 95% CI, 1.04-2.00; 95% PI, 0.86-2.43). The complete-response analyses for TP53 alteration (OR 1.30; 95% CI, 0.01-156.60) and COO (OR 1.27; 95% CI, 0.24-6.61) were statistically uninformative. No study permitted evaluation of complex karyotypes. Conclusions: Biomarker-stratified evidence after CD19 CAR T-cell therapy is sparse and inconsistently reported. DHL/THL status and non-GCB/activated B-cell-like (ABC) COO showed exploratory survival signals, whereas the TP53 and COO complete-response analyses were uninformative. These biomarkers remain hypothesis-generating rather than validated predictors of CAR T-cell outcome, and standardized, prospective biomarker-stratified reporting is needed.

Despite the proven efficacy of KRAS G12C inhibitors (KRAS G12Ci) in solid tumors, evidence from direct comparisons with standard of care is scarce, and no analysis has investigated the potential immunological basis for differential responses.