Two expert-curated databases exclusively licensed through QIAGEN link sequence-level somatic mutation data to detailed molecular information about functional and clinical impacts, as well as implications for druggability and relevant clinical trials. The two databases, the Catalogue Of Somatic Mutations In Cancer (COSMIC) and the Human Somatic Mutation Database (HSMD), enable biopharmaceutical researchers to avoid pitfalls in early cancer drug discovery, confidently qualify candidate drug targets, and accelerate indication expansion and repurposing of existing cancer therapies.
In this blog, learn more about the high-level applications of using COSMIC and HSMD in cancer drug discovery and development pipelines.
The Catalogue of Somatic Mutations in Cancer (COSMIC)
The Catalogue Of Somatic Mutations In Cancer (COSMIC) is the most detailed and comprehensive resource for exploring the effect of somatic mutations in human cancer. Developed and maintained by Wellcome Sanger Institute, the latest release, COSMIC v99 (December 2023), includes over 6 million coding mutations across 1.5 million tumor samples, curated from over 29,000 publications. In addition to coding mutations, COSMIC covers all the genetic mechanisms by which somatic mutations promote cancer, including non-coding mutations, gene fusions, copy-number variants and drug-resistance mutations.
COSMIC integrates somatic data from multiple sources published around the world and allows researchers to access and scrutinize information about somatic mutations and their impact in cancer. Over the past two decades, COSMIC, through predominantly manual curation workflows, has been diligently collecting, cleaning, and organizing genomic data and associated metadata from cancer studies published in scientific literature and various bioinformatics sources. This data is then translated into a standardized format, integrated, and made available to the research community through well-structured datasets and user-friendly data exploration websites and tools.
The Human Somatic Mutation Database (HSMD)
The Human Somatic Mutation Database (HSMD) is a relatively new somatic mutation database from QIAGEN (released in 2019) that combines over two decades of expert curation and data from scientific literature, on- and off-label therapies and clinical trials, and real-world clinical oncology cases. In the latest release, HSMD 3.0 (November 2023), the database contains manually curated, detailed molecular information on over 1.8 million somatic variants, with more than 430,000 observed in real clinical cases, as well as data from over 545,000 real-world clinical oncology cases.
Unique to HSMD is the availability of data from clinically observed variants. When a variant has been “clinically observed,” it means QIAGEN’s professional clinical interpretation service (previously N-of-One) has encountered this alteration in a real-world clinical case. For these variants, QIAGEN assesses the clinical and biological relevance and calculates the gene and variant prevalence across observed tumor types.
Easy to search with new content added weekly, HSMD enables researchers to explore key genes or mutations with driving properties or clinical relevance and search for associated treatment options, off-label therapies, resistance markers, and regional and/or disease-specific clinical trials.
Applications of COSMIC and HSMD in cancer drug discovery and development
While similar, COSMIC and HSMD differ in their applications for cancer drug discovery and development. As a result, biopharmaceutical researchers can use both databases to support different workflow stages.
How COSMIC supports exploratory research in cancer drug discovery
COSMIC is a valuable resource for cancer researchers and drug discovery efforts. Here are several ways in which the COSMIC database can be used to support exploratory research in cancer drug discovery:
- Identification of mutations in target genes – COSMIC provides a comprehensive catalog of somatic mutations observed in various cancer types. Researchers can use COSMIC to identify mutations occurring in the gene associated with the drug target. Evaluating the prevalence and distribution of mutations can help assess the potential impact on the function of the target.
- Frequency of mutations across cancer types – Analyzing COSMIC data allows researchers to assess the frequency of mutations in the target gene across different cancer types. Higher mutation frequencies in specific cancer types may indicate the relevance of the target in those cancers, supporting its potential as a drug target.
- Correlation with clinical data – COSMIC integrates clinical data, including patient outcomes. Researchers can correlate mutations in the target gene with clinical parameters such as patient survival, response to treatment, or disease progression. Positive correlations may suggest the potential significance of the target in predicting clinical outcomes.
- Functional impact of mutations – COSMIC provides information on the functional impact of specific mutations. Understanding whether mutations in the target gene are driver mutations (contributing to cancer development) or passenger mutations (incidental changes) is crucial. Driver mutations are more likely to validate the target as a potential therapeutic intervention.
- Validation across datasets – Researchers can cross-validate findings from COSMIC by comparing them with data from other sources, such as The Cancer Genome Atlas (TCGA) or other cancer genomics databases. Consistency across multiple datasets strengthens the validity of the target.
- Exploration of drug response data – COSMIC includes data on drug response, allowing researchers to explore how cancer cell lines with specific mutations in the target gene respond to different drugs. Assessing drug response data helps predict potential therapeutic strategies and identifies drugs that may be effective against cancers with specific mutations in the target.
- Integration with pathway analysis – COSMIC provides information on pathways associated with mutated genes. Researchers can integrate this data with pathway analysis tools to understand the broader biological context of the target. Pathway analysis helps identify potential interactions and dependencies that can further validate the significance of the target.
How HSMD supports cancer drug clinical development and post-market research
HSMD is a valuable resource for biopharmaceutical researchers, facilitating the confident evaluation of cancer-related genetic variations by granting access to real-world data. Here are several ways in which HSMD supports cancer drug clinical development and post-market research.
- Identify clinical function of somatic mutations – HSMD enables researchers to easily search and explore mutational characteristics across genes, synthesize key findings from drug labels, clinical trials, and professional guidelines, and receive detailed annotations for each observed variant.
- Conduct research use only (RUO) studies – Researchers can leverage HSMD to deepen their understanding of disease mechanisms at the molecular level. RUO studies can explore how specific genetic alterations contribute to disease initiation, progression, and resistance, providing insights into potential therapeutic interventions.
- Clinical trial optimization – HSMD contribute significantly to clinical trial optimization by facilitating patient recruitment, informing trial design, and providing valuable insights throughout the trial lifecycle.
- Patient stratification – The real-world, de-identified patient data in HSMD enables the identification of eligible patients based on specific criteria for clinical trials. Improved patient identification streamlines recruitment efforts, accelerates trial enrollment, and reduces the time and costs associated with the initiation phase.
- Clinical trial feasibility assessment – With clinical trial data that can be segmented by geographic location, HSMD can used to assess the feasibility of conducting a clinical trial at specific sites or within particular patient populations. Understanding patient demographics, disease prevalence, and historical treatment patterns aids in identifying suitable trial locations and estimating recruitment potential.
- Regulatory submission and approval – HSMD data can complement traditional clinical trial data in regulatory submissions, providing additional evidence of a treatment’s effectiveness and safety. Regulatory agencies increasingly recognize the value of real-world evidence in supporting decision-making during drug approval processes.
- Companion diagnostic design – Users can search HSMD by disease and receive a ranked list of associated genes to help design custom assays that enable better prediction of response and resistance to specific therapies.
- Drug repurposing: HSMD enables the analysis of the frequency and distribution of somatic mutations across various cancer types. The database also provides a catalog of drugs employed in the treatment of patients with specific mutations, along with available response data. Using this information, researchers can explore potential new indications for existing cancer drugs.
Transform targets into precision cancer therapies
COSMIC and HSMD are two expert-curated databases licensed exclusively through QIAGEN that enable biopharmaceutical companies to improve the drug discovery process, develop more effective clinical trials, and enhance the treatment of rare cancers. To learn more about how your research team can use COSMIC and HSMD, click the link below for a free trial and personal consultation with our biopharmaceutical research experts.