Keyword: Cancer

ABSTRACT: Precision oncology seeks to identify patient-specific therapeutic vulnerabilities; however, conventional genomic profiling is limited by intratumoral heterogeneity and its inability to distinguish functional driver alterations from passenger mutations, often resulting in incomplete prediction of therapeutic response. Recently, the combination of CRISPR functional genomics with single-cell multi-omics has proven to be a paradigm-shifting strategy for understanding context-specific cancer vulnerabilities by causal functional interrogation. The aim of this review is to critically examine recent progress in the integration of these technologies for discovering vulnerabilities in cancer, and introduces a new conceptual model, called the Integrated Functional Precision Oncology (IFPO) Framework, that brings together functional genomic perturbation, single-cell multi-omics, computational systems biology, and clinical translation. Literature was retrieved from Pubmed, Web of Science and Google Scholar and peer reviewed studies published between 2020 and 2025. Key findings from historic and recent research were analyzed to pinpoint methodological innovations, translational studies, limitations, and areas in need of further research. The results reveal that the integrated CRISPR–single-cell platforms, such as Perturb-seq, CROP-seq, and ECCITE-seq, can be used to causally interrogate gene function at the single-cell level, allowing for the identification of context-dependent essential genes, synthetic lethal interactions, regulatory networks, and therapeutic resistance mechanisms. All the evidence suggests that therapeutic response is not merely a function of genomic alterations but also the dynamic interplay between genomic alterations, cellular state, epigenetic plasticity, and the tumor microenvironment. The proposed IFPO Framework integrates these findings into a systems-level model that captures the mechanisms by which these functional perturbations, multimodal molecular profiling, and AI-driven integration of data converge to reveal clinically actionable cancer vulnerabilities. This integrated paradigm transforms precision oncology from descriptive molecular profiling to functional systems oncology and offers directions for further progress of precision cancer treatment based on enhanced biomarker discovery, therapeutic target identification, and prospective clinical translation.

ABSTRACT: ABSTRACT
Background: Diethylnitrosamine (DEN) is a nitrosamine derivative with alkylating, carcinogenic, and mutagenic properties that causes major liver damage and acts as a hepatocarcinogen in rodents. Acacia nilotica and Kigelia africana are plants used in local communities to treat wounds and ulcers.
Objective: This study investigated the effect of aqueous extracts of Kigelia africana and Acacia nilotica on alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), and cancer antigen 125 (CA-125) levels in DEN-induced liver cell dysplasia in Wistar rats.
Methods: Forty (40) male Wistar rats, aged 6–8 weeks, were divided into eight (8) groups of five (5) animals each. Liver cell dysplasia was induced with a single intraperitoneal dose of DEN (100 mg/kg) and promoted with oral phenobarbitone (0.25 mg/kg) twice weekly, beginning one week after induction. Group I received clean drinking water; group II received DEN only; group III received DEN + phenobarbitone; groups IV and V received DEN + phenobarbitone + 250 mg/kg and 500 mg/kg of Acacia nilotica respectively; groups VI and VII received DEN + phenobarbitone + 250 mg/kg and 500 mg/kg of Kigelia africana respectively; and group VIII received DEN + phenobarbitone + 10 mg/kg of sorafenib. Blood samples were collected on day 120 for biomarker evaluation, and liver tissue was processed for histopathology.
Results: CEA and CA-125 differed significantly among groups (p < 0.001), although group means largely remained within the physiological reference range; AFP showed no significant difference (p = 0.580). The highest CEA values occurred in the DEN-only and DEN + phenobarbitone groups, while CA-125 was highest in the DEN-only and sorafenib-treated groups. Animals treated with the plant extracts, particularly at the higher dose (500 mg/kg), maintained CEA and CA-125 values close to those of the negative control. Histopathology showed dose-dependent attenuation of DEN-induced changes by both extracts, with the higher dose of Kigelia africana producing near-normal liver architecture.
Conclusion: Both extracts, especially at higher doses, appeared chemoprotective against DEN-induced hepatic changes, supporting further investigation of their underlying mechanisms.

ABSTRACT: Surgery in metastatic cancer has been considered to have a limited role in the treatment of metastatic disease and has generally been reserved for palliative intent. However, as imaging, systemic therapy, surgical techniques, and understanding of the biology of cancer has improved, the role of surgery in the treatment of metastatic disease has evolved. This narrative review will discuss the current state of surgical therapy in metastatic cancer and the indications for such an approach. A discussion of the impact of reducing tumor burden, the concept of oligometastatic disease, and the role of host–tumor interactions will provide a basis for the discussion. The objectives of surgery have evolved from palliation to include longer survival and even potentially curative intent. The primary consideration in the decision to pursue surgical therapy for metastatic disease is proper patient selection, and this requires a thorough evaluation of disease and patient factors, as well as the integration of systemic therapy and other local therapies. While evidence is strongest for metastasectomy in colorectal cancer, there is growing evidence in breast cancer, renal cell carcinoma, lung cancer, and neuroendocrine tumors. As a general rule, the optimal management of metastatic cancer includes a combination of systemic and surgical therapies to maximize benefit for the patient. While there are limitations to the current role of surgical therapy in metastatic cancer, challenges including surgical morbidity, delays in initiation of necessary systemic therapy, and a paucity of high-quality evidence, proper patient selection remains the cornerstone to providing meaningful clinical benefit.

ABSTRACT: Prostate cancer still remains one of the most common cancers in men worldwide, and it is a great therapeutic challenge, especially in the field of immunotherapeutics. The tumour microenvironment (TME) is immunologically “cold” in prostate cancer, and influenced by intrinsic molecular characteristics of the disease such as androgen receptor (AR) signalling, PTEN loss, and lineage plasticity towards neuroendocrine prostate cancer (NEPC). Together, these aspects inhibit antigen presentation, block the entry of cytotoxic T cells and help to establish spatially organised immunosuppressive niches, providing a rational explanation for the clinical variability and partial efficacy of immune-based therapies.
Traditional bulk genomic approaches have provided important insights into tumour biology but are unable to capture the cellular and spatial complexity of tumour–immune interactions. These developments have been spurred by recent advancements in single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics, which allow to detect individual cell subpopulations within intact tumour tissues, such as exhausted T cells co-expressing PD-1, TIM-3, LAG-3 and TIGIT, immunosuppressive SPP1+ macrophages and various cancer-associated fibroblast subpopulations. These technologies have identified specific immune exclusion sites, stromal–epithelial immune silencing barriers, and therapeutic resistance and immune evasion regulatory programs in the context of prostate cancer specifically.
However, there are still many technical challenges that need to be overcome, such as the lack of patient samples and their demographic diversity, data integration, lack of spatial characterisation of bone metastases and difficulties in clinical translation. Comprehensive multi-omics atlases, AI-driven spatial pattern recognition, functional validation of potential targets and prospective clinical trials based on biomarkers are all important areas for future research. They show significant potential for the creation of better, personalized immunotherapeutic treatment for prostate cancer.

ABSTRACT: This study was conducted to investigate histological outcomes of patients with locally advanced colorectal cancer involving the urinary bladder, ureters or prostate. Initial cohort included 45 patients but 10 patients were eliminated from the study due to absence of medical records or non-confirmed colon adenocarcinoma. Finally, the study included 35 patients who underwent colon surgery plus either partial or complete bladder resection, partial ureter resection or prostate resection in time period between 2016 and 2025. Data on patient characteristics and results of histological examination were collected retrospectively. Among patients, who underwent colon surgery plus cystectomy (n=27), only in 48% cases confirmed histological invasion was detected. Overall R0 resection was achieved in 94% cases. These data correspond to literature reviewed findings. True lower urinary tract invasion occurred in approximately half of locally advanced colorectal cancer cases, while en bloc resection achieved high R0 rates, supporting resection when invasion is uncertain.

ABSTRACT: Type 2 diabetes mellitus is associated with an increased risk of several malignancies, prompting interest in the potential oncologic effects of antidiabetic therapies, particularly metformin. This study evaluated cancer-related adverse event reporting associated with metformin compared with other antidiabetic agents using real-world pharmacovigilance data from the FDA Adverse Event Reporting System (FAERS) between Q1 2023 and Q4 2024. A disproportionality analysis was conducted on over 3.2 million reports, including 66,187 metformin cases and 55,257 comparator cases comprising GLP-1 receptor agonists, SGLT2 inhibitors, sulfonylureas, and insulin. Reporting odds ratios (ROR), proportional reporting ratios (PRR), information components (IC), and chi-squared tests were applied across twelve pre-specified cancer types.
Metformin was associated with significantly lower reporting of hepatocellular carcinoma (ROR 0.377, 95% CI 0.181–0.782) and pancreatic carcinoma (ROR 0.669, 95% CI 0.493–0.908). In contrast, increased reporting signals were observed for prostate cancer (ROR 2.065, 95% CI 1.435–2.972), leukaemia (ROR 2.388, 95% CI 1.155–4.939), and breast cancer (ROR 1.404, 95% CI 1.023–1.926). Drug-specific comparisons indicated relatively lower overall cancer reporting for metformin compared with sitagliptin and empagliflozin, but higher reporting compared with insulin. Temporal analyses demonstrated variability in reporting patterns across study quarters.
These findings represent disproportionality signals reflecting reporting associations rather than causal effects and may be influenced by reporting bias, residual confounding, and differences in healthcare utilization. Overall, the results suggest a heterogeneous, cancer-type-specific reporting profile for metformin and highlight the value of pharmacovigilance analyses in generating real-world safety signals. Further confirmation in prospective and mechanistic studies is required.

ABSTRACT: Cervical cancer remains a leading cause of cancer-related mortality in Sub-Saharan Africa, where it disproportionately affects women due to late-stage diagnoses. Despite the availability of preventive measures such as screening and HPV vaccination, uptake remains critically low. This systematic review and meta-analysis aimed to estimate the pooled prevalence and identify key predictors of cervical cancer screening uptake across Sub-Saharan Africa. A comprehensive search of databases including PubMed, Google Scholar, African Journal Online (AJOL) and ScienceDirect identified 27 studies involving a total of 357,586 women. Our results revealed that the overall prevalence of cervical cancer screening uptake was 21.2% (95% CI: 16.2%, 27.2%). Key predictors of uptake included education, healthcare access, awareness of cervical cancer, age, and integration with other health services like HIV care. This study underscores the urgent need for tailored interventions to address barriers such as lack of awareness, financial constraints, and cultural stigma. The findings provide crucial evidence to guide policy and public health strategies aimed at increasing screening rates and reducing the cervical cancer burden in the region.

ABSTRACT: Spatial tumour heterogeneity, which denotes the changes in cellular and molecular attributes across distinct locations within a tumour, significantly influences cancer diagnosis and treatment resistance. The heterogeneity of tumour cells inside a singular mass facilitates tumour development, metastasis, and the ineffectiveness of standard therapy. Comprehending the geographical distribution of tumour cells is crucial for formulating more efficient treatment regimens. Diverse methodologies are employed to investigate spatial heterogeneity, encompassing modern imaging techniques such as MRI, PET, and multiplexed imaging, alongside omics approaches including genomes, transcriptomics, and proteomics. These instruments offer insights into the tumour microenvironment and facilitate the identification of resistant subpopulations. The amalgamation of imaging and genomic data via radiogenomics has emerged as a viable methodology, providing an extensive perspective on the spatial and molecular intricacies of tumours. Principal findings reveal that spatial heterogeneity fosters medication resistance by establishing microenvironments characterised by varying oxygen levels, immunological infiltration, and genetic alterations, hence complicating the efficacy of monotherapy strategies. Hypoxic environments and immunological evasion significantly contribute to treatment resistance. Addressing geographical heterogeneity has the potential to enhance cancer treatments. By analysing the molecular and geographical characteristics of tumours, physicians can customise therapies more efficiently, minimising resistance and improving therapeutic results. This methodology signifies a vital advancement in precision medicine, providing more individualised and efficacious cancer therapies in the future.