Aneesa Sultan

Durvalumab is a selective anti-PD-L1 monoclonal antibody and an emerging perioperative treatment for resectable non-small cell lung cancer (NSCLC). However, its survival benefit, Pathological response, and safety require comprehensive evaluation. A systematic search of PubMed/MEDLINE, Cochrane Library, and Embase (2000-2026) was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Eligible studies evaluated perioperative durvalumab (neoadjuvant, adjuvant, or both) in patients with resectable NSCLC. Primary endpoints included overall survival (OS), event-free survival (EFS), disease-free survival (DFS), major Pathological response (mPR), and Pathological complete response (pCR). Safety outcomes included grade ≥ 3 adverse events (AEs), treatment-emergent AEs (TEAEs), and discontinuation rates. Pooled meta-analysis included overall hazard ratio (HR) and risk ratio (RR) with 95% confidence intervals (CIs) for the specified outcomes. Quality of the included studies was assessed using Cochrane RoB 2.0 and JBI Critical Appraisal Checklist. Fourteen studies were included. Durvalumab treatment showed a significant trend toward improvement of EFS in the perioperative studies (HR 0.69; 95% CI: 0.61-0.78; I² = 0%). The two-arm randomized trials demonstrated increased pCR (RR = 4.16; 95% CI: 3.20-5.41; I² = 0%) and improved mPR (RR = 1.23; 95% CI: 0.12-13.01; I² = 84%) using a random-effects model. Safety outcomes were comparable between groups, with no significant increase in grade ≥ 3 AEs or TEAEs. Subgroup analyses based on treatment timing and setting also supported the main findings of the study. Sensitivity analyses for survival endpoints and mPR addressed the heterogeneity concerns by excluding the studies that contributed most to the differences within the included studies. Durvalumab-based perioperative treatment strategies are associated with favorable survival trends, a robust increase in pCR, and a strong improvement in perioperative mPR across early-stage NSCLC settings.

Early-stage breast cancer (BC) shows heterogeneous recurrence risk. Circulating tumor DNA (ctDNA) is promising non-invasive biomarker for minimal residual disease and recurrence prediction, though prognostic performance varies by assay and context. Eligible studies on ctDNA-based recurrence and survival were identified through comprehensive searches, quality assessed, and analyzed using random-effects meta-analysis to estimate pooled hazard ratios for clinical outcomes. Heterogeneity (I², τ², Cochran's Q), subgroup (detection method or assay type), and sensitivity analyses were performed to examine the consistency and robustness of results. For recurrence-free survival endpoints, the pooled HR was 3.28 [95% CI: 1.81; 5.93], indicating a high risk of recurrence-related events among ctDNA-positive patients, though substantial heterogeneity was observed (I² = 93.3%). Pooled effect sized for overall survival (8.92 HR [0.45; 177.87], I² = 74.7%) and recurrence/relapse (5.21 [0.98; 27.69], I² = 84.4%) indicating substantial heterogeneity. Subgroup analysis showed lower heterogeneity with digital PCR and personalized ctDNA assays, and sensitivity testing confirmed result stability (2.47 [1.89; 3.23], I² = 0%). ctDNA positivity, detected through mutation-based assays strongly associated with increased risk for early recurrence in early-stage BC. Digital PCR and personalized assays demonstrated superior consistency; however, prospective trials are needed to establish its clinical utility.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with five years survival rate less than 5%. In Pakistan, transcriptomic profiling of pancreatic cancer is limited, with most evidence derived from in silico and isolated NGS analyses, highlighting the need for RNA-sequencing-based expression profiling in Pakistani PDAC cohorts. The purpose of this study is to report hub genes that are involved in progression of cancer and can be used as diagnostic and therapeutic markers. Pakistani PDAC RNA-seq dataset was pooled with seven publicly available NCBI-GEO datasets (GSE136569, GSE119794, GSE164665, GSE119224, GSE211398, GSE196009, and GSE40174) to probe common hub genes. The expression of these hub genes in tumor samples was evaluated using Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR) and validated through Whole Exome Sequencing. CDC20, PLK1, BUB1, CDC45, and CDCA5 were concordantly present in seven NCI-GEO Datasets along with Pakistani RNA-seq dataset. These hub genes were upregulated at the initial stages of PDAC. RT-qPCR revealed significant upregulation in Pakistani tumor samples (*P < 0.05, **P < 0.001). WES analysis demonstrates non synonymous pathogenic variants in BUB1. The consistent dysregulated expression of the hub genes across independent NCBI-GEO datasets and the Pakistani RNA-seq cohort suggests their possible robustness across diverse populations and potential utility as broadly applicable biomarkers. These findings offer population-specific insights that may inform future biomarker-guided diagnostic and prognostic stratification of PDAC in Pakistan.

Urologic cancers represent a heterogeneous collection of malignancies of the urinary and male reproductive tracts, including prostate, bladder, adrenal, ureteral, urethral, penile, testicular, and renal cell cancers. This chapter discusses emerging developments and ongoing hurdles in the diagnosis and molecular targeted treatment of these tumors. Special focus is given to the shortcomings of present-day methodologies, such as suboptimal sensitivity and specificity of available biomarkers and a lack of standardization of liquid biopsy and molecular profiling. In addition, integration of next-generation sequence information in the clinic is hamstrung by the complexity of interpretation and infrastructural requirements. Technological hurdles in artificial intelligence-assisted imaging and pathology make early detection and personalized therapy planning increasingly challenging. By comparing these hurdles with emerging developments, the chapter attempts an overview of present scenarios and future prospects in urologic cancer management.

Metastatic cancer remains a major challenge in oncology, often diagnosed late with limited intervention options. This chapter highlights the role of circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) as biomarkers for early detection, diagnosis, and prognosis. Liquid biopsy, a non-invasive method, analyzes blood components like CTCs, which provide insights into tumor heterogeneity and metastatic potential, and ctDNA, which reflects genetic mutations and tumor burden. These biomarkers enable real-time tumor monitoring, aiding in understanding progression, treatment response, residual disease, and resistance mechanisms. Advances in detection methods emphasize their clinical relevance in personalized cancer treatment. Integrating CTCs and ctDNA into oncology could revolutionize management through individualized strategies, enhancing early detection and outcomes. The chapter concludes with challenges and future directions for implementing these biomarkers in precision oncology.

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is the 3 ^rd leading cause of cancer‐related mortalities and has a poor prognosis, with a 5‐year survival of 8%–9%. The major challenge associated with management of PDAC is delayed diagnosis. Diagnosis at an early stage can significantly increase the survival. Therefore, we used multiomics analysis to validate a novel signature biomarker of early‐stage PDAC. The signature was derived from a computational analysis and subsequently validated in the Pakistani patient cohort, including patients with well‐defined early‐stage (I and II) PDAC. Methods: With the aim of validating the signature biomarker ( MUC3A / MUC4 / MUC13 / MUC16 ) as a potent early diagnostic and prognostic marker, a comprehensive analysis of multiomics data of the Pakistani cohort was performed utilizing the integrated whole‐exome sequencing, transcriptome analysis, and RT‐qPCR. Results: The in vitro validation of a signature biomarker in the Pakistani cohort reveals the pathogenic effect of mutations in the key MUC genes and its profound effect on its protein functionality. Among all key MUC genes analyzed in a transcriptomic dataset, only MUC4 exhibits statistically significant differential expression. Finally, RT‐qPCR results demonstrate significant overexpression of all key MUC genes in PDAC blood samples. Conclusion: In conclusion, our findings suggest MUC3A/MUC4/MUC13/MUC16 as robust diagnostic and prognostic biomarkers and liquid biopsy as a noninvasive approach to be integrated into daily clinical practice. This analysis can also be extended to other malignancies.

Background: Advancements in nanoscience have led to a profound paradigm shift in the therapeutic applications of medicinally important natural drugs. The goal of this research is to develop a nano-natural product for efficient cancer treatment. Methods and Results: For this purpose, mesoporous silica nanoparticles (MSNPs) were formulated, characterized, and loaded with caffeine to develop a targeted drug delivery system, i.e., caffeine-coated nanoparticles (CcNPs). In silico docking studies were conducted to examine the binding efficiency of the CcNPs with different apoptotic targets followed by in vitro and in vivo bioassays in respective animal models. Caffeine, administered both as a free drug and in nanomedicine form, along with doxorubicin, was delivered intravenously to a benzene-induced AML model. The anti-leukemic potential was assessed through hematological profiling, enzymatic biomarker analysis, and RT-PCR examination of genetic alterations in leukemia markers. Docking studies show strong inter-molecular interactions between CcNPs and apoptotic markers. In vitro analysis exhibits statistically significant antioxidant activity, whereas in vivo analysis exhibits normalization of the genetic expression of leukemia biomarkers STMN1 and S1009A, accompanied by the restoration of the hematological and morphological traits of leukemic blood cells in nanomedicine-treated rats. Likewise, a substantial improvement in hepatic and renal biomarkers is also observed. In addition to these findings, the nanomedicine successfully normalizes the elevated expression of GAPDH and mTOR induced by exposure to benzene. Further, the nanomedicine downregulates pro-survival components of the NF-kappa B pathway and upregulated P53 expression. Additionally, in the TRAIL pathway, it enhances the expression of pro-apoptotic players TRAIL and DR5 and downregulates the anti-apoptotic protein cFLIP. Conclusions: Our data suggest that MSNPs loaded with caffeine, i.e., CcNP/nanomedicine, can potentially inhibit transformed cell proliferation and induce pro-apoptotic TRAIL machinery to counter benzene-induced leukemia. These results render our nanomedicine as a potentially excellent therapeutic agent against AML.

Benzene, a potent carcinogen, is known to cause acute myeloid leukaemia. While chemotherapy is commonly used for cancer treatment, its side effects have prompted scientists to explore natural products that can mitigate the haematotoxic effects induced by chemicals. One area of interest is nano-theragnostics, which aims to enhance the therapeutic potential of natural products. This study aimed to enhance the effects of methanolic extracts from Ocimum basilicum, Rosemarinus officinalis, and Thymus vulgaris by loading them onto silica nanobeads (SNBs) for targeted delivery to mitigate the benzene-induced haematotoxic effects. The SNBs, 48 nm in diameter, were prepared using a chemical method and were then loaded with the plant extracts. The plant-extract-loaded SNBs were then coated with carboxymethyl cellulose (CMC). The modified SNBs were characterized using various techniques such as scanning electron microscopy (SEM), X-ray diffraction (XRD), UV–visible spectroscopy, and Fourier transform infrared (FTIR) spectroscopy. The developed plant-extract-loaded and CMC-modified SNBs were administered intravenously to benzene-exposed rats, and haematological and histopathological profiling was conducted. Rats exposed to benzene showed increased liver and spleen weight, which was mitigated by the plant-extract-loaded SNBs. The differential white blood cell (WBC) count was higher in rats with benzene-induced haematotoxicity, but this count decreased significantly in rats treated with plant-extract-loaded SNBs. Additionally, blast cells observed in benzene-exposed rats were not found in rats treated with plant-extract-loaded SNBs. The SNBs facilitated targeted drug delivery of the three selected medicinal herbs at low doses. These results suggest that SNBs have promising potential as targeted drug delivery agents to mitigate haematotoxic effects induced by benzene in rats.

Breast cancer (BC) continues to be the most common cancer in the women worldwide. Since estrogen receptor (ER)-positive BC accounts for the majority of newly diagnosed cases, endocrine therapy is advised to utilize either tamoxifen (Tam) or aromatase inhibitors. The use of Tam as a monotherapy or in conjunction with an aromatase inhibitor following two or three years of endocrine therapy has long been recommended. When used adjuvantly, Tam medication reduces BC mortality and relapses, while it extends survival times in metastatic BC when used in conjunction with other treatments. Unfortunately, the efficiency of Tam varies considerably. This study was conducted to explore the influence of genetic polymorphisms in CYP2C19 gene on Tam’s pharmacogenetics and pharmacokinetics in estrogen-positive BC patients. Data from healthy, unrelated individuals ( n = 410; control group) and ER-positive BC patients ( n = 430) receiving 20 mg of Tam per day were recruited. Steady-state plasma concentrations of Tam and its three metabolites were quantified using the high-performance liquid chromatography in the patients. The CYP2C19 polymorphisms were genotyped using an Amplification Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR) approach. More than 65% of healthy individuals were extensive metabolizers (*1/*1) for CYP2C19, whereas more than 70% of ER-positive BC patients were rapid and ultrarapid metabolizers (*1/17*, *17/17*). The polymorphism CYP2C19*17 is significantly associated with higher 4-hydroxytamoxifen (4-OH-Tam). Patients with the *17/*17 genotype exhibited 1- to 1.5-fold higher 4-OH-Tam, which was also high in patients with the *1/*2 and *2/*2 genotypes.