Abstract
The clinical efficacy of therapeutic monoclonal antibodies for breast and colorectal cancer has greatly contributed to the improvement of patients’ outcomes by individualizing their treatments according to their genomic background. However, primary or acquired resistance to treatment reduces its efficacy. In this context, the identification of biomarkers predictive of drug response would support research and development of new alternative treatments. Biomarkers play a major role in the genomic revolution, supporting disease diagnosis and treatment decision-making. Currently, several molecular biomarkers of treatment response for breast and colorectal cancer have been described. However, information on these biomarkers is scattered across several resources, and needs to be identified, collected and properly integrated to be fully exploited to inform monitoring of drug response in patients. Therefore, there is a need of resources that offer biomarker data in a harmonized manner to the user to support the identification of actionable biomarkers of response to treatment in cancer. ResMarkerDB was developed as a comprehensive resource of biomarkers of drug response in colorectal and breast cancer. It integrates data of biomarkers of drug response from existing repositories, and new data extracted and curated from the literature (referred as ResCur). ResMarkerDB currently features 266 biomarkers of diverse nature. Twenty-five percent of these biomarkers are exclusive of ResMarkerDB. Furthermore, ResMarkerDB is one of the few resources offering non-coding DNA data in response to drug treatment. The database contains more than 500 biomarker-drug-tumour associations, covering more than 100 genes. ResMarkerDB provides a web interface to facilitate the exploration of the current knowledge of biomarkers of response in breast and colorectal cancer. It aims to enhance translational research efforts in identifying actionable biomarkers of drug response in cancer.
Highlights
The heterogeneity of cancer at different levels, namely genetic, proteomic, morphological and even at the tumour microenvironment, poses challenges to its diagnosis and treatment [1]
While all the monoclonal antibodies (mAbs) used for breast cancer treatment target HER2, the mAbs currently used for colorectal cancer treatment target Epidermal Growth Factor Receptor (EGFR) or Vascular Endothelial Growth Factor (VEGF)
ResMarkerDB was developed as a web-based platform to facilitate exploration of current knowledge of biomarkers of response to Food and Drug Administration (FDA)-approved mAbs in breast and colorectal cancer
Summary
The heterogeneity of cancer at different levels, namely genetic, proteomic, morphological and even at the tumour microenvironment, poses challenges to its diagnosis and treatment [1]. We have developed ResMarkerDB as a centralized repository that harmonizes data of biomarkers of response to FDA-approved mAbs for breast and colorectal cancer To this end, we have integrated data from four publicly available repositories with information extracted from the literature by text mining followed by expert curation. We conducted a process of data homogenization and standardization using ontologies and controlled vocabularies This process was performed for each entity annotated in ResMarkerDB: biomarker, drug, tumour type, response, evidence level, source and statement. For each combination biomarker-drug-tumourresponse we identified a sentence in the original publication that supported the association (the ‘supporting statement’) These statements were identified by text mining and manually selected when they were not provided by the source databases. The ncRNAs were analysed for their association with breast and colorectal cancer using DisGeNET version 5.0 [26]
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