| Application: | 44288, A meta-investigation of combinatorial mutation signatures in broad disease categories |
| Title: | Systematic drug repurposing to enable precision medicine: A case study in breast cancer |
| Size: | 5.5 MB |
| Archived: | 18 Feb 2021 |
| Stability: | Complete |
| Personal: | No individual-level data |
Return 3134
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Notes
Precision medicine and drug repurposing provide an opportunity to ameliorate the challenges of declining pharmaceutical R&D productivity, rising costs of new drugs, and poor patient response rates to existing medications. Multifactorial disease signatures provide unique insights into the architecture of complex disease populations that can be used to better stratify patient groups, aiding the delivery of precision medicine. Methods: Analysis of a complex disease (breast cancer) population was undertaken to identify the combinations of single-nucleotide polymorphisms that are associated with different disease subgroups. Target genes associated with the disease risk of these subgroups were examined, followed by identification and evaluation of existing active chemical leads as drug repurposing candidates. Results: One hundred and seventy-five disease-associated gene targets relevant to different subpopulations of breast cancer patients were identified. Twenty-three of these genes were prioritized as both promising novel drug targets and repurposing candidates. Two targets, P4HA2 and TGM2, have high repurposing potential and a strong mechanistic link to breast cancer. Conclusions: This study showed that detailed analysis of combinatorial genomic (and other) features can be used to accurately stratify patient populations and identify highly plausible drug repurposing candidates systematically across all disease-associated targets.Application 44288
A meta-investigation of combinatorial mutation signatures in broad disease categories
The proposed study aims to address three research questions: * Are there genetic defect patterns common to broad categories of disease such as all cancers, all psychiatric disorders, or all musculoskeletal disorders? * Conversely, are there genetic patterns that help protect people against broad categories of disease, such as cancer or cardiovascular disease? * Are there genotypic variant signatures allowing stratification of patients that could inform the risk of developing a disorder and likelihood of drug therapy response? The proposed research would improve our understanding of the genomic basis of disease formation (or disease prevention). We hope to identify individual genetic defects or combinatorial defect clusters that are commonly associated with broad categories of disease, that is, found in significantly higher numbers of patients compared to healthy controls. Similarly, we hope to identify protective signatures that are found in many more healthy controls compared to afflicted individuals. In addition, we hope to develop new improved ways of identifying patients at risk of developing a disease or its complications, and enable patients to be treated with a drug therapy regimen that is tailored to their individual needs. Successful results would help future researchers identify means to increase human longevity and wellness by manipulating genetic mechanisms involved in broad categories of disease. Through follow-on studies, researchers may identify new drugs that work across broad categories of disease. Such drugs with broad applicability may cost less to develop, test, and bring to market, thus helping everyone afflicted with those diseases. Tailoring therapies to patients' individual needs may significantly reduce the burden on the healthcare system through reduced side effects due to drug interaction or lack of therapy response, leading to hospital admissions. The project duration is 24 months.
| Lead investigator: | Dr Sayoni Das |
| Lead institution: | PrecisionLife Ltd |
2 related Returns
| Return ID | App ID | Description | Archive Date |
|---|---|---|---|
| 3252 | 44288 | Analysis of Genetic Host Response Risk Factors in Severe COVID-19 Patients | 19 Mar 2021 |
| 3251 | 44288 | Identification and Analysis of Shared Risk Factors in Sepsis and High Mortality Risk COVID-19 Patients | 19 Mar 2021 |
1 Publication
| Pub ID | Title | Author(s) | Year | Journal |
|---|---|---|---|---|
| 3135 | Systematic drug repurposing to enable precision medicine: A case study in breast cancer | Taylor et al. | 2019 | Digital Medicine (2019) |
Enabling scientific discoveries that improve human health