Advances and challenges in drug repurposing in precision therapeutics of colorectal cancer

Table 1 Summary of databases related to drug repurposing

Database	Description	Applications
ChEMBL	Bioactivity database	Contains bioactivity data of small molecule compounds, associated drug targets, biological data, etc., for drug development
Drug target commons	Drug target database	Provides drug and target interaction data, including target selectivity, mechanism of action and experimental data, for drug target selection and development
Binding database	Binding affinity database	Includes binding affinity data between small molecule compounds and proteins, such as inhibitory concentration (IC50), binding constant (Kd), for drug screening
Protein data bank	Structured database	Stores three-dimensional structural information of biological macromolecules (e.g. proteins, nucleic acids, and complexes) for use in molecular modeling and structural analysis
Sider	Drug side effects database	Provides information on drug related side effects, showing the adverse reactions and mechanisms of action of known compounds, for safety assessment
OMIM	Genetic diseases and mutations database	Contains information related to human genes and genetic diseases, including disease phenotypes, gene mutations, and genetic relationships
DrugBank	Comprehensive drug database	Integrates information on pharmaceutical chemistry, biological targets, metabolic pathways, and mechanisms of action, it is an important tool for pharmacology and medicinal chemistry
BioVU DNA Databank	Biological sample database	Contains information about a patient’s DNA, linked to clinical data, for genetics and precision medicine research
United Kingdom Biobank	Cohort and biobank	A national-level repository of genomic data, health records, and lifestyle data for epidemiological and disease association studies
Drug Repurposing Hub	Drug repurposing database	Provides data on drugs that have been approved or failed, as well as information on their potential in new indications
Repurpose database	Drug indications repurpose database	Covers data on drugs or indications that have been reported and focuses on revealing new uses of drugs through data mining
Pathway commons	Path integration database	Collects and integrates relational networks of multiple biological pathways, such as metabolic, signaling, and gene regulatory networks, for systems biology and network analysis
KEGG pathways	Pathway database	Provides data on the biological pathways of genomes, metabolism, diseases and drugs, and is an important reference resource for biology and drug development
Pharmaco database	Drug sensitivity database	Contains sensitivity data on the response of cancer cell lines to drugs for anticancer drug screening and personalized treatment research
Cell model passports	Cell model database	Provides cell model information for cancer and other disease research, including genomic data, omics data, and cell origin information
Xeva	Drug response modeling tools	Tools for modeling xenograft data, such as PDX models, to provide drug efficacy predictions and inter-model comparisons
FAERS	Adverse drug event database	An adverse drug event reporting system administered by the FDA, containing adverse event reports and drug safety monitoring information
Sentinel system	Drug safety database	A signal monitoring system developed by the United States FDA to monitor the safety of drugs, vaccines and medical devices on the market
OncoPDSS	Decision support system for personalized oncology chemotherapy	It is used to assist in the selection of appropriate chemotherapy drugs and treatment regimens based on patient genomic information to enhance precise tumor therapy

FDA: Food and Drug Administration; KEGG: Kyoto Encyclopedia of Genes and Genomes.

Table 2 Recent advances and drugs in drug repurposing for colorectal cancer treatment

Pathways	Drugs	Purposes
Wnt/β-catenin signaling pathway	Pyrotinib	TKI inhibitor to degrade β-catenin
	Risedronate	ADC to target therapeutic sites
EGFR/RAS/MAPK signaling pathway	Aspirin	NSAID to inhibit EGFR activity
	Simvastatin	Lipid-lowering drug to inhibit MAPK activity
PI3K/AKT/mTOR signaling pathway	MET	Antidiabetic drug to activate AMPK/NF-κB signaling pathway
Tumor inflammation and immune regulation	Tocilizumab	MRA to block IL-6 signaling
	Aspirin and pembrolizumab	Combinations to modulate tumor microenvironment
Metabolic reprogramming	2-DG	Glycolysis inhibitor to reprogram glucose metabolism
	Metformin	Antidiabetic drug to reduce lactate production
Epigenetic regulation	Vorinostat	HDAC inhibitor to induce histone hyperacetylation
Anti-angiogenesis	Bevacizumab	Monoclonal antibody to target VEGF
	Thalidomide	Treatment of nausea in pregnant women to inhibit VEGF pathway

EGFR: Epidermal growth factor receptor; MAPK: Mitogen-activated protein kinase; PI3K: Phosphatidylinositol 3-kinase; AKT: Protein kinase B; mTOR: Mammalian target of rapamycin; MET: Metformin hydrochloride; MRA: Tocilizumab; 2-DG: 2-Deoxy-D-glucose; TKI: Tyrosine kinase inhibitor; ADC: Antibody-drug conjugates; NSAID: Nonsteroidal anti-inflammatory drugs; AMPK: Adenosine 5’-monophosphate-activated protein kinase; NF-κB: Nuclear factor kappa-B; IL: Interleukin; HDAC: Histone deacetylase; VEGF: Vascular endothelial growth factor.