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
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
Cancers are caused by the accumulation of genetic alterations. Since this accumulation takes time, the incidence of most cancers is thought to increase exponentially with age. However, careful measurements of the age-specific incidence shows that the specific incidence for many forms of cancer rises with age to a maximum, then decreases. This decrease in the age-specific incidence with age is an anomaly. Understanding this anomaly should lead to a better understanding of how tumors develop and grow. Here I derive the shape of the age-specific incidence, showing that it should follow the shape of a Weibull distribution. Measurements indicate that the age-specific incidence for colon cancer does indeed follow a Weibull distribution. This analysis leads to the interpretation that for colon cancer two sub-populations exist in the general population: a susceptible population and an immune population. Colon tumors will only occur in the susceptible population. This analysis is consistent with the developmental origins of disease hypothesis and generalizable to many other common forms of cancer.
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.
Data science has become increasingly essential for the production of official statistics, as it enables the automated collection, processing, and analysis of large amounts of data. With such data science practices in place, it enables more timely, more insightful and more flexible reporting. However, the quality and integrity of data-science-driven statistics rely on the accuracy and reliability of the data sources and the machine learning techniques that support them. In particular, changes in data sources are inevitable to occur and pose significant risks that are crucial to address in the context of machine learning for official statistics. This paper gives an overview of the main risks, liabilities, and uncertainties associated with changing data sources in the context of machine learning for official statistics. We provide a checklist of the most prevalent origins and causes of changing data sources; not only on a technical level but also regarding ownership, ethics, regulation, and public perception. Next, we highlight the repercussions of changing data sources on statistical reporting. These include technical effects such as concept drift, bias, availability, validity, accur
Despite the spectacular achievements of molecular biology in the second half of the twentieth century and the crucial advances it permitted in cancer research, the fight against cancer has brought some disillusions. It is nowadays more and more apparent that getting a global picture of the very diverse and interlinked aspects of cancer development necessitates, in synergy with these achievements, other perspectives and investigating tools. In this undertaking, multidisciplinary approaches that include quantitative sciences in general and physics in particular play a crucial role. This `focus on' collection contains 19 articles representative of the diversity and state-of-the-art of the contributions that physics can bring to the field of cancer research.
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
Photoacoustic imaging (PAI) is a novel medical imaging modality that uses the advantages of the spatial resolution of ultrasound imaging and the high contrast of pure optical imaging. Analytical algorithms are usually employed to reconstruct the photoacoustic (PA) images as a result of their simple implementation. However, they provide a low accurate image. Model-based (MB) algorithms are used to improve the image quality and accuracy while a large number of transducers and data acquisition are needed. In this paper, we have combined the theory of compressed sensing (CS) with MB algorithms to reduce the number of transducer. Smoothed version of L0-norm (SL0) was proposed as the reconstruction method, and it was compared with simple iterative reconstruction (IR) and basis pursuit. The results show that S$\ell_0$ provides a higher image quality in comparison with other methods while a low number of transducers were. Quantitative comparison demonstrates that, at the same condition, the SL0 leads to a peak-signal-to-noise ratio for about two times of the basis pursuit.
As the data volume of astronomical imaging surveys rapidly increases, traditional methods for image anomaly detection, such as visual inspection by human experts, are becoming impractical. We introduce a machine-learning-based approach to detect poor-quality exposures in large imaging surveys, with a focus on the DECam Legacy Survey (DECaLS) in regions of low extinction (i.e., $E(B-V)<0.04$). Our semi-supervised pipeline integrates a vision transformer (ViT), trained via self-supervised learning (SSL), with a k-Nearest Neighbor (kNN) classifier. We train and validate our pipeline using a small set of labeled exposures observed by surveys with the Dark Energy Camera (DECam). A clustering-space analysis of where our pipeline places images labeled in ``good'' and ``bad'' categories suggests that our approach can efficiently and accurately determine the quality of exposures. Applied to new imaging being reduced for DECaLS Data Release 11, our pipeline identifies 780 problematic exposures, which we subsequently verify through visual inspection. Being highly efficient and adaptable, our method offers a scalable solution for quality control in other large imaging surveys.
Although cancer is known to be characterized by several unifying biological hallmarks, systems biology has had limited success in identifying molecular signatures present in in all types of cancer. The current availability of rich data sets from many different cancer types provides an opportunity for thorough computational data mining in search of such common patterns. Here we report the identification of 18 "pan-cancer" molecular signatures resulting from analysis of data sets containing values from mRNA expression, microRNA expression, DNA methylation, and protein activity, from twelve different cancer types. The membership of many of these signatures points to particular biological mechanisms related to cancer progression, suggesting that they represent important attributes of cancer in need of being elucidated for potential applications in diagnostic, prognostic and therapeutic products applicable to multiple cancer types.
There is a widening recognition that cancer cells are products of complex developmental processes. Carcinogenesis and metastasis formation are increasingly described as systems-level, network phenomena. Here we propose that malignant transformation is a two-phase process, where an initial increase of system plasticity is followed by a decrease of plasticity at late stages of carcinogenesis as a model of cellular learning. We describe the hallmarks of increased system plasticity of early, tumor initiating cells, such as increased noise, entropy, conformational and phenotypic plasticity, physical deformability, cell heterogeneity and network rearrangements. Finally, we argue that the large structural changes of molecular networks during cancer development necessitate a rather different targeting strategy in early and late phase of carcinogenesis. Plastic networks of early phase cancer development need a central hit, while rigid networks of late stage primary tumors or established metastases should be attacked by the network influence strategy, such as by edgetic, multi-target, or allo-network drugs. Cancer stem cells need special diagnosis and targeting, since their dormant and rapid
Purpose: Tumor-associated vasculature differs from healthy blood vessels by its chaotic architecture and twistedness, which promotes treatment resistance. Measurable differences in these attributes may help stratify patients by likely benefit of systemic therapy (e.g. chemotherapy). In this work, we present a new category of radiomic biomarkers called quantitative tumor-associated vasculature (QuanTAV) features, and demonstrate their ability to predict response and survival across multiple cancers, imaging modalities, and treatment regimens. Experimental Design: We segmented tumor vessels and computed mathematical measurements of twistedness and organization on routine pre-treatment radiology (CT or contrast-enhanced MRI) from 558 patients, who received one of four first-line chemotherapy-based therapeutic intervention strategies for breast (n=371) or non-small cell lung cancer (NSCLC, n=187). Results: Across 4 chemotherapy-based treatment strategies, classifiers of QuanTAV measurements significantly (p<.05) predicted response in held out testing cohorts alone (AUC=0.63-0.71) and increased AUC by 0.06-0.12 when added to models of significant clinical variables alone. QuanTAV ris
Recently, there has been great interest in developing Artificial Intelligence (AI) enabled computer-aided diagnostics solutions for the diagnosis of skin cancer. With the increasing incidence of skin cancers, low awareness among a growing population, and a lack of adequate clinical expertise and services, there is an immediate need for AI systems to assist clinicians in this domain. A large number of skin lesion datasets are available publicly, and researchers have developed AI-based image classification solutions, particularly deep learning algorithms, to distinguish malignant skin lesions from benign lesions in different image modalities such as dermoscopic, clinical, and histopathology images. Despite the various claims of AI systems achieving higher accuracy than dermatologists in the classification of different skin lesions, these AI systems are still in the very early stages of clinical application in terms of being ready to aid clinicians in the diagnosis of skin cancers. In this review, we discuss advancements in the digital image-based AI solutions for the diagnosis of skin cancer, along with some challenges and future opportunities to improve these AI systems to support d
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
Interpreting traditional B-mode ultrasound images can be challenging due to image artifacts (e.g., shadowing, speckle), leading to low sensitivity and limited diagnostic accuracy. While Magnetic Resonance Imaging (MRI) has been proposed as a solution, it is expensive and not widely available. Furthermore, most biopsies are guided by Transrectal Ultrasound (TRUS) alone and can miss up to 52% cancers, highlighting the need for improved targeting. To address this issue, we propose ProsDectNet, a multi-task deep learning approach that localizes prostate cancer on B-mode ultrasound. Our model is pre-trained using radiologist-labeled data and fine-tuned using biopsy-confirmed labels. ProsDectNet includes a lesion detection and patch classification head, with uncertainty minimization using entropy to improve model performance and reduce false positive predictions. We trained and validated ProsDectNet using a cohort of 289 patients who underwent MRI-TRUS fusion targeted biopsy. We then tested our approach on a group of 41 patients and found that ProsDectNet outperformed the average expert clinician in detecting prostate cancer on B-mode ultrasound images, achieving a patient-level ROC-AUC
Recent tumor genome sequencing confirmed that one tumor often consists of multiple cell subpopulations (clones) which bear different, but related, genetic profiles such as mutation and copy number variation profiles. Thus far, one tumor has been viewed as a whole entity in cancer functional studies. With the advances of genome sequencing and computational analysis, we are able to quantify and computationally dissect clones from tumors, and then conduct clone-based analysis. Emerging technologies such as single-cell genome sequencing and RNA-Seq could profile tumor clones. Thus, we should reconsider how to conduct cancer systems biology studies in the genome sequencing era. We will outline new directions for conducting cancer systems biology by considering that genome sequencing technology can be used for dissecting, quantifying and genetically characterizing clones from tumors. Topics discussed in Part 1 of this review include computationally quantifying of tumor subpopulations; clone-based network modeling, cancer hallmark-based networks and their high-order rewiring principles and the principles of cell survival networks of fast-growing clones.
Micro Abstract: A recent study from GLOBOCAN disclosed that during 2018 two million women worldwide had been diagnosed from breast cancer. This study presents a computer-aided diagnosis system based on convolutional neural networks as an alternative diagnosis methodology for breast cancer diagnosis with thermal images. Experimental results showed that lower false-positives and false-negatives classification rates are obtained when data pre-processing and data augmentation techniques are implemented in these thermal images. Background: There are many types of breast cancer screening techniques such as, mammography, magnetic resonance imaging, ultrasound and blood sample tests, which require either, expensive devices or personal qualified. Currently, some countries still lack access to these main screening techniques due to economic, social or cultural issues. The objective of this study is to demonstrate that computer-aided diagnosis(CAD) systems based on convolutional neural networks (CNN) are faster, reliable and robust than other techniques. Methods: We performed a study of the influence of data pre-processing, data augmentation and database size versus a proposed set of CNN mode
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.
Embryology has long played a foundational role in shaping our scientific understanding of animal evolution. In recent decades, growing evidence has also highlighted its role in cancer. Despite the indisputable similarities between embryonic development and cancer, there has been limited discussion on the profound embryological implications for the disease. This article explores the understanding of cancer as an embryological and evolutionary phenomenon, offering a fresh perspective on the disease and discussing immediate consequences in the search for therapeutic approaches
Prostate cancer (PCa) is one of the most common cancers in men worldwide. Bi-parametric MRI (bp-MRI) and clinical variables are crucial for PCa identification and improving treatment decisions. However, this process is subjective to expert interpretations. Furthermore, most existing computer-aided diagnosis methods focus on imaging-based models, overlooking the clinical context and suffering from data scarcity, limiting their ability to learn robust representations. We propose a geometric multimodal Foundation Model (FM), named MFM-Geom, that learns representations from bp-MRI and clinical reports, encoding visual findings and information from the context of clinical variables. In the representations classification head, the approach leverages symmetric positive definite (SPD) matrices and Riemannian deep learning to integrate imaging-text representations from a biomedical multimodal FM. Using 10% of the training data, MFM-Geom outperformed baseline class token embedding-based classification (+8.3%, AUC-PR of 90.67). Generalization on external dataset confirmed the robustness of fine-tuning biomedical FM, achieving an AUC-PR of 90.6.