Personalised use of repurposed non-anticancer drugs in colorectal cancer based on up-regulated signalling pathways: A real world cohort feasibility study
Abstract
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Background:
Targeting signaling pathways in colorectal cancers is a common therapeutic strategy. In addition to targeted drugs, non- anticancer drugs approved for use in other health conditions can inhibit key pathways. De novo tumor transcriptome analysis can identify patient-specific up- and down-regulated transcripts, based on which the corresponding repurposed drugs can be used in synergistic combinations with standard of care (SoC) regimens.
Methods:
This retrospective study was conducted on a real-world cohort of 459 colorectal cancer cases (218 females, 241 males; median age 56 years) who had taken Exacta multi-omics tumor profiling for selection of personalized treatments. Transcriptome analysis was performed as part of the evaluations to determine up and down-regulated gene transcripts for selecting targeted, endocrine, and cytotoxic anticancer agents as well as non-anticancer (repurposed) drugs and phytochemicals that could be used for tandem targeting of the dysregulated signaling pathways, as indicated in the table below.
Results:
Transcriptome analysis of this cohort revealed dysregulation of ≥1 pathway in 391 patients (85.2%). MAPKs (n = 244, 53.2%) and MMPs (n = 210, 45.8%) were most frequently upregulated. Celecoxib (n = 292, 63.6%), Atorvastatin (n = 255, 55.6%), and Doxycycline (n = 208, 45.3%) were the most frequently indicated repurposed drugs for targeting the identified dysregulated pathways. Potential indications for ≥1 repurposed drugs were seen…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 391 participants or records.
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