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The discovery and development of novel therapeutic products for the treatment of malignancy is vitally important to those physicians responsible for the management of cancer patients. A description of the ongoing efforts at the National Cancer Institute (NCI) is intended to provide insight into those complex processes necessary to accomplish this mission. An update on the NCI's revised cancer screen is accompanied by a brief summary of those new agents scheduled to be entered into clinical investigation in the near future. The tremendous potential advantages and challenges associated with the use of a molecular approach to cancer drug design are discussed. Despite the differences of opinion that may exist regarding the optimal strategies for accomplishing the mission, there is no disagreement regarding the importance of the effort to find effective new therapies for cancer patients.

With the emergence of genomic profiling technologies and selective molecular targeted therapies, biomarkers play an increasingly important role in the clinical management of cancer patients. Single gene/protein or multi-gene "signature"-based assays have been introduced to measure specific molecular pathway deregulations that guide therapeutic decision-making as predictive biomarkers. Genome-based prognostic biomarkers are also available for several cancer types for potential incorporation into clinical prognostic staging systems or practice guidelines. However, there is still a large gap between initial biomarker discovery studies and their clinical translation due to the challenges in the process of cancer biomarker development. In this review we summarize the steps of biomarker development, highlight key issues in successful validation and implementation, and overview representative examples in the oncology field. We also discuss regulatory issues and future perspectives in the era of big data analysis and precision medicine.

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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

Quantum machine learning offers a promising new paradigm for computational biology by leveraging quantum mechanical principles to enhance cancer classification, biomarker discovery, and bioinformatics diagnostics. In this study, we apply QML to identify subtype specific biomarkers for lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), the two predominant forms of non-small cell lung cancer. Our methodology involves a two-phase process: in Phase 1, differential expression analysis and methylation analysis between tumor and normal samples allows us to identify LUAD-specific and LUSC-specific genes, revealing potential prognostic biomarkers for cancer subtypes. Phase 2 focuses on developing a quantum classifier capable of distinguishing between LUAD and LUSC tumors, as well as between tumor and normal samples. This classifier not only enhances diagnostic precision but also demonstrates the quantum advantage in processing large-scale multiomic datasets. Our results consistently demonstrated that Sample3, representing the combined gene set, achieved the highest overall predictive performance in all metrics. These results demonstrate that QML provides an effective and sc

Motivation: Uncovering the genomic causes of cancer, known as cancer driver genes, is a fundamental task in biomedical research. Cancer driver genes drive the development and progression of cancer, thus identifying cancer driver genes and their regulatory mechanism is crucial to the design of cancer treatment and intervention. Many computational methods, which take the advantages of computer science and data science, have been developed to utilise multiple types of genomic data to reveal cancer drivers and their regulatory mechanism behind cancer development and progression. Due to the complexity of the mechanistic insight of cancer genes in driving cancer and the fast development of the field, it is necessary to have a comprehensive review about the current computational methods for discovering different types of cancer drivers. Results: We survey computational methods for identifying cancer drivers from genomic data. We categorise the methods into three groups, methods for single driver identification, methods for driver module identification, and methods for identifying personalised cancer drivers. We also conduct a case study to compare the performance of the current methods. W

Cancer is known as a disease mainly caused by gene alterations. Discovery of mutated driver pathways or gene sets is becoming an important step to understand molecular mechanisms of carcinogenesis. However, systematically investigating commonalities and specificities of driver gene sets among multiple cancer types is still a great challenge, but this investigation will undoubtedly benefit deciphering cancers and will be helpful for personalized therapy and precision medicine in cancer treatment. In this study, we propose two optimization models to \emph{de novo} discover common driver gene sets among multiple cancer types (ComMDP) and specific driver gene sets of one certain or multiple cancer types to other cancers (SpeMDP), respectively. We first apply ComMDP and SpeMDP to simulated data to validate their efficiency. Then, we further apply these methods to 12 cancer types from The Cancer Genome Atlas (TCGA) and obtain several biologically meaningful driver pathways. As examples, we construct a common cancer pathway model for BRCA and OV, infer a complex driver pathway model for BRCA carcinogenesis based on common driver gene sets of BRCA with eight cancer types, and investigate s

Anti-cancer drug discoveries have been serendipitous, we sought to present the Open Molecular Graph Learning Benchmark, named CandidateDrug4Cancer, a challenging and realistic benchmark dataset to facilitate scalable, robust, and reproducible graph machine learning research for anti-cancer drug discovery. CandidateDrug4Cancer dataset encompasses multiple most-mentioned 29 targets for cancer, covering 54869 cancer-related drug molecules which are ranged from pre-clinical, clinical and FDA-approved. Besides building the datasets, we also perform benchmark experiments with effective Drug Target Interaction (DTI) prediction baselines using descriptors and expressive graph neural networks. Experimental results suggest that CandidateDrug4Cancer presents significant challenges for learning molecular graphs and targets in practical application, indicating opportunities for future researches on developing candidate drugs for treating cancers.

While skin cancer is the most diagnosed form of cancer in men and women, with more cases diagnosed each year than all other cancers combined, sufficiently early diagnosis results in very good prognosis and as such makes early detection crucial. While radiomics have shown considerable promise as a powerful diagnostic tool for significantly improving oncological diagnostic accuracy and efficiency, current radiomics-driven methods have largely rely on pre-defined, hand-crafted quantitative features, which can greatly limit the ability to fully characterize unique cancer phenotype that distinguish it from healthy tissue. Recently, the notion of discovery radiomics was introduced, where a large amount of custom, quantitative radiomic features are directly discovered from the wealth of readily available medical imaging data. In this study, we present a novel discovery radiomics framework for skin cancer detection, where we leverage novel deep multi-column radiomic sequencers for high-throughput discovery and extraction of a large amount of custom radiomic features tailored for characterizing unique skin cancer tissue phenotype. The discovered radiomic sequencer was tested against 9,152 b

Prostate cancer is the most diagnosed form of cancer in Canadian men, and is the third leading cause of cancer death. Despite these statistics, prognosis is relatively good with a sufficiently early diagnosis, making fast and reliable prostate cancer detection crucial. As imaging-based prostate cancer screening, such as magnetic resonance imaging (MRI), requires an experienced medical professional to extensively review the data and perform a diagnosis, radiomics-driven methods help streamline the process and has the potential to significantly improve diagnostic accuracy and efficiency, and thus improving patient survival rates. These radiomics-driven methods currently rely on hand-crafted sets of quantitative imaging-based features, which are selected manually and can limit their ability to fully characterize unique prostate cancer tumour phenotype. In this study, we propose a novel \textit{discovery radiomics} framework for generating custom radiomic sequences tailored for prostate cancer detection. Discovery radiomics aims to uncover abstract imaging-based features that capture highly unique tumour traits and characteristics beyond what can be captured using predefined feature mo

Radiomics has proven to be a powerful prognostic tool for cancer detection, and has previously been applied in lung, breast, prostate, and head-and-neck cancer studies with great success. However, these radiomics-driven methods rely on pre-defined, hand-crafted radiomic feature sets that can limit their ability to characterize unique cancer traits. In this study, we introduce a novel discovery radiomics framework where we directly discover custom radiomic features from the wealth of available medical imaging data. In particular, we leverage novel StochasticNet radiomic sequencers for extracting custom radiomic features tailored for characterizing unique cancer tissue phenotype. Using StochasticNet radiomic sequencers discovered using a wealth of lung CT data, we perform binary classification on 42,340 lung lesions obtained from the CT scans of 93 patients in the LIDC-IDRI dataset. Preliminary results show significant improvement over previous state-of-the-art methods, indicating the potential of the proposed discovery radiomics framework for improving cancer screening and diagnosis.

While lung cancer is the second most diagnosed form of cancer in men and women, a sufficiently early diagnosis can be pivotal in patient survival rates. Imaging-based, or radiomics-driven, detection methods have been developed to aid diagnosticians, but largely rely on hand-crafted features which may not fully encapsulate the differences between cancerous and healthy tissue. Recently, the concept of discovery radiomics was introduced, where custom abstract features are discovered from readily available imaging data. We propose a novel evolutionary deep radiomic sequencer discovery approach based on evolutionary deep intelligence. Motivated by patient privacy concerns and the idea of operational artificial intelligence, the evolutionary deep radiomic sequencer discovery approach organically evolves increasingly more efficient deep radiomic sequencers that produce significantly more compact yet similarly descriptive radiomic sequences over multiple generations. As a result, this framework improves operational efficiency and enables diagnosis to be run locally at the radiologist's computer while maintaining detection accuracy. We evaluated the evolved deep radiomic sequencer (EDRS) di

Neural-guided equation discovery systems use a data set as prompt and predict an equation that describes the data set without extensive search. However, if the equation does not meet the user's expectations, there are few options for getting other equation suggestions without intensive work with the system. To fill this gap, we propose Residuals for Equation Discovery (RED), a post-processing method that improves a given equation in a targeted manner, based on its residuals. By parsing the initial equation to a syntax tree, we can use node-based calculation rules to compute the residual for each subequation of the initial equation. It is then possible to use this residual as new target variable in the original data set and generate a new prompt. If, with the new prompt, the equation discovery system suggests a subequation better than the old subequation on a validation set, we replace the latter by the former. RED is usable with any equation discovery system, is fast to calculate, and is easy to extend for new mathematical operations. In experiments on 53 equations from the Feynman benchmark, we show that it not only helps to improve all tested neural-guided systems, but also all t

Background. The Drug Discovery Unit (DDU) of Cancer Research UK (CRUK) is using the software Dotmatics for storage and analysis of scientific data during drug discovery process. Whilst the data include event logs, time stamps, activities, and user information are mostly sitting in the database without fully utilising their potential value. Aims. This dissertation aims at extracting knowledge from event logs data which recorded during drug discovery process, to capture the operational business process of the DDU of Cancer Research UK (CRUK) as it was being executed. It provides the evaluations and methodologies of drawing the process mining panoramic models for the drug discovery process. Thus by enabling the DDU to maximise its efficiency in reviewing its resources and works allocations, patients will benefit from more new treatments faster. Conclusion. Management of organisations can be benefit from the process mining methodologies. Disco is excellent for non-experts on management purposes. ProM is great for expert on research purposes. However, the process mining is not once and for all but is a regular operation management process. Indeed, event logs needs to be understand more

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

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

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

Recent advances in large language models (LLMs) have shown great potential to accelerate drug discovery. However, the specialized nature of biochemical data often necessitates costly domain-specific fine-tuning, posing major challenges. First, it hinders the application of more flexible general-purpose LLMs for cutting-edge drug discovery tasks. More importantly, it limits the rapid integration of the vast amounts of scientific data continuously generated through experiments and research. Compounding these challenges is the fact that real-world scientific questions are typically complex and open-ended, requiring reasoning beyond pattern matching or static knowledge retrieval.To address these challenges, we propose CLADD, a retrieval-augmented generation (RAG)-empowered agentic system tailored to drug discovery tasks. Through the collaboration of multiple LLM agents, CLADD dynamically retrieves information from biomedical knowledge bases, contextualizes query molecules, and integrates relevant evidence to generate responses - all without the need for domain-specific fine-tuning. Crucially, we tackle key obstacles in applying RAG workflows to biochemical data, including data heteroge

Alterations in cancer genomes strongly influence clinical responses to treatment and in many instances are potent biomarkers for response to drugs. The Genomics of Drug Sensitivity in Cancer (GDSC) database (www.cancerRxgene.org) is the largest public resource for information on drug sensitivity in cancer cells and molecular markers of drug response. Data are freely available without restriction. GDSC currently contains drug sensitivity data for almost 75 000 experiments, describing response to 138 anticancer drugs across almost 700 cancer cell lines. To identify molecular markers of drug response, cell line drug sensitivity data are integrated with large genomic datasets obtained from the Catalogue of Somatic Mutations in Cancer database, including information on somatic mutations in cancer genes, gene amplification and deletion, tissue type and transcriptional data. Analysis of GDSC data is through a web portal focused on identifying molecular biomarkers of drug sensitivity based on queries of specific anticancer drugs or cancer genes. Graphical representations of the data are used throughout with links to related resources and all datasets are fully downloadable. GDSC provides a unique resource incorporating large drug sensitivity and genomic datasets to facilitate the discovery of new therapeutic biomarkers for cancer therapies.