Cancer data, particularly cancer incidence and mortality, are fundamental to understand the cancer burden, to set targets for cancer control and to evaluate the evolution of the implementation of a cancer control policy. However, the complexity of data collection, classification, validation and processing result in cancer incidence figures often lagging two to three years behind the calendar year. In response, national or regional population-based cancer registries (PBCRs) are increasingly interested in methods for forecasting cancer incidence. However, in many countries there is an additional difficulty in projecting cancer incidence as regional registries are usually not established in the same year and therefore cancer incidence data series between different regions of a country are not harmonised over time. This study addresses the challenge of forecasting cancer incidence with incomplete data at both regional and national levels. To achieve this, we propose the use of multivariate spatio-temporal shared component models that jointly model mortality data and available cancer incidence data. We evaluate the performance of these multivariate models using lung cancer incidence dat
India faces a significant cancer burden, with an incidence-to-mortality ratio indicating that nearly three out of five individuals diagnosed with cancer succumb to the disease. While the limitations of physical healthcare infrastructure are widely acknowledged as a primary challenge, concerted efforts by government and healthcare agencies are underway to mitigate these constraints. However, given the country's vast geography and high population density, it is imperative to explore alternative soft infrastructure solutions to complement existing frameworks. Artificial Intelligence agents are increasingly transforming problem-solving approaches across various domains, with their application in medicine proving particularly transformative. In this perspective, we examine the potential role of AI agents in advancing nuclear medicine for cancer research, diagnosis, and management in India. We begin with a brief overview of AI agents and their capabilities, followed by a proposed agent-based ecosystem that can address prevailing sustainability challenges in India nuclear medicine.
The objective of this research is to introduce a network specialized in predicting drugs that can be repurposed by investigating real-world evidence sources, such as clinical trials and biomedical literature. Specifically, it aims to generate drug combination therapies for complex diseases (e.g., cancer, Alzheimer's). We present a multilayered network medicine approach, empowered by a highly configured ChatGPT prompt engineering system, which is constructed on the fly to extract drug mentions in clinical trials. Additionally, we introduce a novel algorithm that connects real-world evidence with disease-specific signaling pathways (e.g., KEGG database). This sheds light on the repurposability of drugs if they are found to bind with one or more protein constituents of a signaling pathway. To demonstrate, we instantiated the framework for breast cancer and found that, out of 46 breast cancer signaling pathways, the framework identified 38 pathways that were covered by at least two drugs. This evidence signals the potential for combining those drugs. Specifically, the most covered signaling pathway, ID hsa:2064, was covered by 108 drugs, some of which can be combined. Conversely, the s
In today's complex healthcare landscape, the pursuit of delivering optimal patient care while navigating intricate economic dynamics poses a significant challenge for healthcare service providers (HSPs). In this already complex dynamics, the emergence of clinically promising personalized medicine based treatment aims to revolutionize medicine. While personalized medicine holds tremendous potential for enhancing therapeutic outcomes, its integration within resource-constrained HSPs presents formidable challenges. In this study, we investigate the economic feasibility of implementing personalized medicine. The central objective is to strike a balance between catering to individual patient needs and making economically viable decisions. Unlike conventional binary approaches to personalized treatment, we propose a more nuanced perspective by treating personalization as a spectrum. This approach allows for greater flexibility in decision-making and resource allocation. To this end, we propose a mathematical framework to investigate our proposal, focusing on Bladder Cancer (BC) as a case study. Our results show that while it is feasible to introduce personalized medicine, a highly effici
In this review, we discuss recent advances on the plasticity of cancer stem cells and highlight their relevance to understand the metastatic process and to guide therapeutic interventions. Recent results suggest that the strict hierarchical structure of cancer cell populations advocated by the cancer stem cell model must be reconsidered since the depletion of cancer stem cells leads the other tumor cells to switch back into the cancer stem cell phenotype. This plasticity has important implications for metastasis since migrating cells do not need to be cancer stem cells in order to seed a metastasis. We also discuss the important role of the immune system and the microenvironment in modulating phenotypic switching and suggest possible avenues to exploit our understanding of this process to develop an effective strategy for precision medicine.
Cancer has become one of the most widespread diseases in the world. Specifically, breast cancer is diagnosed more often than any other type of cancer. However, breast cancer patients and their individual tumors are often unique. Identifying the underlying genetic phenotype can lead to precision (personalized) medicine. Tailoring medical treatment strategies to best fit the needs of individual patients can dramatically improve their health. Such an approach requires sufficient knowledge of the patients and the diseases, which is currently unavailable to practitioners. This study focuses on breast cancer and proposes a novel two-stage clustering method to partition patients into hierarchical groups. The first stage is broad grouping, which is based on phenotypes such as demographic information and clinical features. The second stage is fine grouping based on genomic characteristics, such as copy number variation and somatic mutation, of patients in a subgroup resulting from the first stage. Generally, this framework offers a mechanism to mix multiple forms of data, both phenotypic and genomic, to most effectively define individual patients for personalized predictions. This method pr
Model Medicine is the science of understanding, diagnosing, treating, and preventing disorders in AI models, grounded in the principle that AI models -- like biological organisms -- have internal structures, dynamic processes, heritable traits, observable symptoms, classifiable conditions, and treatable states. This paper introduces Model Medicine as a research program, bridging the gap between current AI interpretability research (anatomical observation) and the systematic clinical practice that complex AI systems increasingly require. We present five contributions: (1) a discipline taxonomy organizing 15 subdisciplines across four divisions -- Basic Model Sciences, Clinical Model Sciences, Model Public Health, and Model Architectural Medicine; (2) the Four Shell Model (v3.3), a behavioral genetics framework empirically grounded in 720 agents and 24,923 decisions from the Agora-12 program, explaining how model behavior emerges from Core--Shell interaction; (3) Neural MRI (Model Resonance Imaging), a working open-source diagnostic tool mapping five medical neuroimaging modalities to AI interpretability techniques, validated through four clinical cases demonstrating imaging, compari
In recent years, cancer genome sequencing and other high-throughput studies of cancer genomes have generated many notable discoveries. In this review, Novel genomic alteration mechanisms, such as chromothripsis (chromosomal crisis) and kataegis (mutation storms), and their implications for cancer are discussed. Genomic alterations spur cancer genome evolution. Thus, the relationship between cancer clonal evolution and cancer stems cells is commented. The key question in cancer biology concerns how these genomic alterations support cancer development and metastasis in the context of biological functioning. Thus far, efforts such as pathway analysis have improved the understanding of the functional contributions of genetic mutations and DNA copy number variations to cancer development, progression and metastasis. However, the known pathways correspond to a small fraction, plausibly 5-10%, of somatic mutations and genes with an altered copy number. To develop a comprehensive understanding of the function of these genomic alterations in cancer, an integrative network framework is proposed and discussed. Finally, the challenges and the directions of studying cancer omic data using an in
Breast cancer screening plays a pivotal role in early detection and subsequent effective management of the disease, impacting patient outcomes and survival rates. This study aims to assess breast cancer screening rates nationwide in the United States and investigate the impact of social determinants of health on these screening rates. Data on mammography screening at the census tract level for 2018 and 2020 were collected from the Behavioral Risk Factor Surveillance System. We developed a large dataset of social determinants of health, comprising 13 variables for 72337 census tracts. Spatial analysis employing Getis-Ord Gi statistics was used to identify clusters of high and low breast cancer screening rates. To evaluate the influence of these social determinants, we implemented a random forest model, with the aim of comparing its performance to linear regression and support vector machine models. The models were evaluated using R2 and root mean squared error metrics. Shapley Additive Explanations values were subsequently used to assess the significance of variables and direction of their influence. Geospatial analysis revealed elevated screening rates in the eastern and northern U
With the increasing interest in deploying Artificial Intelligence in medicine, we previously introduced HAIM (Holistic AI in Medicine), a framework that fuses multimodal data to solve downstream clinical tasks. However, HAIM uses data in a task-agnostic manner and lacks explainability. To address these limitations, we introduce xHAIM (Explainable HAIM), a novel framework leveraging Generative AI to enhance both prediction and explainability through four structured steps: (1) automatically identifying task-relevant patient data across modalities, (2) generating comprehensive patient summaries, (3) using these summaries for improved predictive modeling, and (4) providing clinical explanations by linking predictions to patient-specific medical knowledge. Evaluated on the HAIM-MIMIC-MM dataset, xHAIM improves average AUC from 79.9% to 90.3% across chest pathology and operative tasks. Importantly, xHAIM transforms AI from a black-box predictor into an explainable decision support system, enabling clinicians to interactively trace predictions back to relevant patient data, bridging AI advancements with clinical utility.
We present a general computational theory of cancer and its developmental dynamics. The theory is based on a theory of the architecture and function of developmental control networks which guide the formation of multicellular organisms. Cancer networks are special cases of developmental control networks. Cancer results from transformations of normal developmental networks. Our theory generates a natural classification of all possible cancers based on their network architecture. Each cancer network has a unique topology and semantics and developmental dynamics that result in distinct clinical tumor phenotypes. We apply this new theory with a series of proof of concept cases for all the basic cancer types. These cases have been computationally modeled, their behavior simulated and mathematically described using a multicellular systems biology approach. There are fascinating correspondences between the dynamic developmental phenotype of computationally modeled {\em in silico} cancers and natural {\em in vivo} cancers. The theory lays the foundation for a new research paradigm for understanding and investigating cancer. The theory of cancer networks implies that new diagnostic methods
Lung cancer is the primary cause of cancer-related mortality, claiming approximately 1.79 million lives globally in 2020, with an estimated 2.21 million new cases diagnosed within the same period. Among these, Non-Small Cell Lung Cancer (NSCLC) is the predominant subtype, characterized by a notably bleak prognosis and low overall survival rate of approximately 25% over five years across all disease stages. However, survival outcomes vary considerably based on the stage at diagnosis and the therapeutic interventions administered. Recent advancements in artificial intelligence (AI) have revolutionized the landscape of lung cancer prognosis. AI-driven methodologies, including machine learning and deep learning algorithms, have shown promise in enhancing survival prediction accuracy by efficiently analyzing complex multi-omics data and integrating diverse clinical variables. By leveraging AI techniques, clinicians can harness comprehensive prognostic insights to tailor personalized treatment strategies, ultimately improving patient outcomes in NSCLC. Overviewing AI-driven data processing can significantly help bolster the understanding and provide better directions for using such syste
Motivation: Standard genome-wide association studies in cancer genomics rely on statistical significance with multiple testing correction, but systematically fail in underpowered cohorts. In TCGA breast cancer (n=967, 133 deaths), low event rates (13.8%) create severe power limitations, producing false negatives for known drivers and false positives for large passenger genes. Results: We developed a five-criteria computational framework integrating causal inference (inverse probability weighting, doubly robust estimation) with orthogonal biological validation (expression, mutation patterns, literature evidence). Applied to TCGA-BRCA mortality analysis, standard Cox+FDR detected zero genes at FDR<0.05, confirming complete failure in underpowered settings. Our framework correctly identified RYR2 -- a cardiac gene with no cancer function -- as a false positive despite nominal significance (p=0.024), while identifying KMT2C as a complex candidate requiring validation despite marginal significance (p=0.047, q=0.954). Power analysis revealed median power of 15.1% across genes, with KMT2C achieving only 29.8% power (HR=1.55), explaining borderline statistical significance despite stron
Prostate cancer (PCa) is the most prevalent cancer among men in the United States, accounting for nearly 300,000 cases, 29\% of all diagnoses and 35,000 total deaths in 2024. Traditional screening methods such as prostate-specific antigen (PSA) testing and magnetic resonance imaging (MRI) have been pivotal in diagnosis, but have faced limitations in specificity and generalizability. In this paper, we explore the potential of enhancing PCa gland segmentation using a novel MRI modality called synthetic correlated diffusion imaging (CDI$^s$). We employ several state-of-the-art deep learning models, including U-Net, SegResNet, Swin UNETR, Attention U-Net, and LightM-UNet, to segment prostate glands from a 200 CDI$^s$ patient cohort. We find that SegResNet achieved superior segmentation performance with a Dice-Sorensen coefficient (DSC) of $76.68 \pm 0.8$. Notably, the Attention U-Net, while slightly less accurate (DSC $74.82 \pm 2.0$), offered a favorable balance between accuracy and computational efficiency. Our findings demonstrate the potential of deep learning models in improving prostate gland segmentation using CDI$^s$ to enhance PCa management and clinical support.
Nanorobots are a promising development in targeted drug delivery and the treatment of neurological disorders, with potential for crossing the blood-brain barrier (BBB). These small devices leverage advancements in nanotechnology and bioengineering for precise navigation and targeted payload delivery, particularly for conditions like brain tumors, Alzheimer's disease, and Parkinson's disease. Recent progress in artificial intelligence (AI) and machine learning (ML) has improved the navigation and effectiveness of nanorobots, allowing them to detect and interact with cancer cells through biomarker analysis. This study presents a new reinforcement learning (RL) framework for optimizing nanorobot navigation in complex biological environments, focusing on cancer cell detection by analyzing the concentration gradients of surrounding biomarkers. We utilize a computer simulation model to explore the behavior of nanorobots in a three-dimensional space with cancer cells and biological barriers. The proposed method uses Q-learning to refine movement strategies based on real-time biomarker concentration data, enabling nanorobots to autonomously navigate to cancerous tissues for targeted drug d
Lung cancer (LC) is a leading cause of cancer-related mortality in the United States. Accurate prediction of LC mortality rates is crucial for guiding targeted interventions and addressing health disparities. Although traditional regression-based models have been commonly used, explainable machine learning models may offer enhanced predictive accuracy and deeper insights into the factors influencing LC mortality. This study applied three models: random forest (RF), gradient boosting regression (GBR), and linear regression (LR) to predict county-level LC mortality rates across the United States. Model performance was evaluated using R-squared and root mean squared error (RMSE). Shapley Additive Explanations (SHAP) values were used to determine variable importance and their directional impact. Geographic disparities in LC mortality were analyzed through Getis-Ord (Gi*) hotspot analysis. The RF model outperformed both GBR and LR, achieving an R2 value of 41.9% and an RMSE of 12.8. SHAP analysis identified smoking rate as the most important predictor, followed by median home value and the percentage of the Hispanic ethnic population. Spatial analysis revealed significant clusters of el
Cancer is increasingly perceived as a systems-level, network phenomenon. The major trend of malignant transformation can be described as a two-phase process, where an initial increase of network plasticity is followed by a decrease of plasticity at late stages of tumor development. The fluctuating intensity of stress factors, like hypoxia, inflammation and the either cooperative or hostile interactions of tumor inter-cellular networks, all increase the adaptation potential of cancer cells. This may lead to the bypass of cellular senescence, and to the development of cancer stem cells. We propose that the central tenet of cancer stem cell definition lies exactly in the indefinability of cancer stem cells. Actual properties of cancer stem cells depend on the individual "stress-history" of the given tumor. Cancer stem cells are characterized by an extremely large evolvability (i.e. a capacity to generate heritable phenotypic variation), which corresponds well with the defining hallmarks of cancer stem cells: the possession of the capacity to self-renew and to repeatedly re-build the heterogeneous lineages of cancer cells that comprise a tumor in new environments. Cancer stem cells rep
With the advances in artificial intelligence (AI), data-driven algorithms are becoming increasingly popular in the medical domain. However, due to the nonlinear and complex behavior of many of these algorithms, decision-making by such algorithms is not trustworthy for clinicians and is considered a black-box process. Hence, the scientific community has introduced explainable artificial intelligence (XAI) to remedy the problem. This systematic scoping review investigates the application of XAI in breast cancer detection and risk prediction. We conducted a comprehensive search on Scopus, IEEE Explore, PubMed, and Google Scholar (first 50 citations) using a systematic search strategy. The search spanned from January 2017 to July 2023, focusing on peer-reviewed studies implementing XAI methods in breast cancer datasets. Thirty studies met our inclusion criteria and were included in the analysis. The results revealed that SHapley Additive exPlanations (SHAP) is the top model-agnostic XAI technique in breast cancer research in terms of usage, explaining the model prediction results, diagnosis and classification of biomarkers, and prognosis and survival analysis. Additionally, the SHAP mo
Background Precise prediction of cancer types is vital for cancer diagnosis and therapy. Important cancer marker genes can be inferred through predictive model. Several studies have attempted to build machine learning models for this task however none has taken into consideration the effects of tissue of origin that can potentially bias the identification of cancer markers. Results In this paper, we introduced several Convolutional Neural Network (CNN) models that take unstructured gene expression inputs to classify tumor and non-tumor samples into their designated cancer types or as normal. Based on different designs of gene embeddings and convolution schemes, we implemented three CNN models: 1D-CNN, 2D-Vanilla-CNN, and 2D-Hybrid-CNN. The models were trained and tested on combined 10,340 samples of 33 cancer types and 731 matched normal tissues of The Cancer Genome Atlas (TCGA). Our models achieved excellent prediction accuracies (93.9-95.0%) among 34 classes (33 cancers and normal). Furthermore, we interpreted one of the models, known as 1D-CNN model, with a guided saliency technique and identified a total of 2,090 cancer markers (108 per class). The concordance of differential e
What does Artificial Intelligence (AI) have to contribute to health care? And what should we be looking out for if we are worried about its risks? In this paper we offer a survey, and initial evaluation, of hopes and fears about the applications of artificial intelligence in medicine. AI clearly has enormous potential as a research tool, in genomics and public health especially, as well as a diagnostic aid. It's also highly likely to impact on the organisational and business practices of healthcare systems in ways that are perhaps under-appreciated. Enthusiasts for AI have held out the prospect that it will free physicians up to spend more time attending to what really matters to them and their patients. We will argue that this claim depends upon implausible assumptions about the institutional and economic imperatives operating in contemporary healthcare settings. We will also highlight important concerns about privacy, surveillance, and bias in big data, as well as the risks of over trust in machines, the challenges of transparency, the deskilling of healthcare practitioners, the way AI reframes healthcare, and the implications of AI for the distribution of power in healthcare ins