Faculty of Medicine and Surgery
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Item Unraveling the tumor microenvironment: Insights into cancer metastasis and therapeutic strategies(Cancer Letters, 2024) El-Tanani, Mohamed; Rabbani , Syed Arman; Babiker, Rasha; Rangraze, Imran; Kapre, Sumedha; Palakurthi, Sushesh Srivastsa; Alnuqaydan, Abdullah M.; Aljabali, Alaa A.; Rizzo, Manfredi; El-Tanani, Yahia; Tambuwala, Murtaza M.This comprehensive review delves into the pivotal role of the tumor microenvironment (TME) in cancer metastasis and therapeutic response, offering fresh insights into the intricate interplay between cancer cells and their surrounding milieu. The TME, a dynamic ecosystem comprising diverse cellular and acellular elements, not only fosters tumor progression but also profoundly affects the efficacy of conventional and emerging cancer therapies. Through nuanced exploration, this review illuminates the multifaceted nature of the TME, elucidating its capacity to engender drug resistance via mechanisms such as hypoxia, immune evasion, and the establishment of physical barriers to drug delivery. Moreover, it investigates innovative therapeutic approaches aimed at targeting the TME, including stromal reprogramming, immune microenvironment modulation, extracellular matrix (ECM)-targeting agents, and personalized medicine strategies, highlighting their po tential to augment treatment outcomes. Furthermore, this review critically evaluates the challenges posed by the complexity and heterogeneity of the TME, which contribute to variable therapeutic responses and potentially unintended consequences. This underscores the need to identify robust biomarkers and advance predictive models to anticipate treatment outcomes, as well as advocate for combination therapies that address multiple facets of the TME. Finally, the review emphasizes the necessity of an interdisciplinary approach and the integration of cutting-edge technologies to unravel the intricacies of the TME, thereby facilitating the development of more effective, adaptable, and personalized cancer treatments. By providing critical insights into the current state of TME research and its implications for the future of oncology, this review highlights the dynamic and evolving landscape of this field.Item Metformin: A Dual-Role Player in Cancer Treatment and Prevention: A Comprehensive Systematic Review and Meta-Analysis(Medicina, 2025) Rangraze, Imran; Wali, Adil Farooq; El-Tanani , Mohamed; Patni , Mohamed Anas; Rabbani, Syed Arman; Babiker, Rasha; Satyam, Shakta Mani; El-Tanani, Yahia; Rizzo, ManfrediBackground and Objectives: Metformin is said to reduce the incidences and deaths resulting from cancer in patients suffering from type 2 diabetes mellitus, but the results have been inconsistent. Perform a systematic review and meta-analysis concentrating on the different outcomes of several cancers while taking into account the impact of metformin use. Materials and Methods: As of 15 October 2024, the literature for Medline, Embase, and WebofScience was systematically searched. ROBINS-I and the RoB 2 tool were used for assessing the risk of bias in observational studies and randomized controlled trials (RCTs), respectively. The strength of the evidence with respect to the GRADE criteria was checked. Random effects meta-analyses were conducted alongside sensitivity analyses, subgroup analyses, and meta-regressions. By utilizing funnel plots as well as Egger’s test and trim-and-fill analysis, publication bias was evaluated. Results: In total, 65 studies were included in the final analyses: Metformin intake was linked to a lower risk of cancer (RR 0.72; 95% CI: 0.64–0.81, I2 = 45%). Significant reductions were observed in breast cancer (RR 0.68; 95% CI: 0.55–0.83) and colorectal cancers (RR 0.62; 95% CI: 0.51–0.76). Evidence certainty fluctuated from moderate to low, though analyses confirmed the results. Plofs funded the publication bias, but adjustment in trim-and-fill did not change the outcome significantly. Conclusions: Metformin intake seems to lower the chances of developing several types of cancers, especially breast and colorectal cancers, but the observational designs hinder determining the causal factors for observational studies. There is a need for large RCTsItem Advancements in non-invasive biomarkers for detection and monitoring of breast cancer recurrence(SCIENCE PROGRESS, 2025) El-Tanani, Yahia; El-Tanani, Mohamed; Rabbani, Syed Arman; Babiker, Rasha; Satyam, Shakta ManiBreast cancer recurrence remains a major cause of mortality, with up to 30% of early stage patients relapsing as incurable metastatic disease. Conventional surveillance with imaging and serum markers (CA15–3, CEA) lacks the sensitivity and specificity to detect minimal residual disease. This narrative review examines non-invasive biomarkers such as circulating tumor DNA (ctDNA), circulating tumor cells (CTCs) and exosomes and the technologies enhancing their performance. Droplet digital PCR and next-generation sequencing detect ctDNA at allele frequencies below 0.1%, identifying molecular relapse a median of 10–12 months before radiologic progression. Microfluidic and affinity-based platforms isolate CTCs with over 75% sensitivity in metastatic settings. Nanoengineered sensors and standardized workflows improve exosome isolation, revealing miRNA and protein signatures predictive of recurrence. Proteomic and metabolomic profiling iden tify dysregulated metabolic pathways and protein networks, offering functional insights that complement molecular assays. Integrative multi-omics approaches merge genomic, transcriptomic, proteomic and metabolomic data; machine-learning frameworks detect subtle patterns and correlations, enabling dynamic, personalized surveillance. By detect ing molecular and functional biomarkers early, clinicians can tailor therapy, monitor treatment response and intervene promptly. Challenges include low analyte abundance, assay variability, high costs and lack of standardized protocols, limiting clinical adoption. Prospective validation in large cohorts is critical. We highlight ongoing clinical trials such as ctDNA-guided adjuvant therapy and CTC-driven stratification studies that aim to establish clinical utility. Non-invasive biomarker platforms could shift breast cancer fol low-up from reactive detection to proactive intervention, ultimately improving survival and quality of life through personalized, real-time monitoring.