Network biology in drug development
Drugs are compounds that interact with biological targets, which are typically key proteins that are involved in specific signaling pathways in the cell. Complex diseases, like cancer and autoimmune disease, are often caused by alterations in multi-protein signaling pathways, so drugs can treat these diseases by correcting the pathways via stimulation or blockage of key proteins. There is an inherent degree of variability in complex diseases, however, and two patients with the same disease may have slightly different alterations in the same signaling pathway – these subtle differences explain the variation in effectiveness of certain drugs between patients.
The ability to observe changes in the organization of the PPI network in, for example, a tumor cell can allow for a better understanding of why a drug might be effective in one patient versus another. Scrutinizing the relative abundance of proteins in the aberrant signaling pathway is a new means to differentiate and predict drug-responsive patients and non-responsive patients.
Clinical trials
Dynemo provides analytical services to improve results from clinical efficacy studies. For studies in which gene-expression microarray data has been collected, the sponsor can upload de-identified raw microarray data (with corresponding drug-response profiles) via a secure web-portal to Dynemo’s servers. Dynemo will then analyze the data and consult the sponsor on the results, which may include: a PPI network organization pattern that corresponds to drug-responsiveness or several patterns that are associated with a varying degree of responsiveness; and detailed information about which protein-protein interactions differ between states.
The benefit to the sponsor is a drug that is highly efficacious in a particular subpopulation, which, for example, could make the difference between a third-line therapeutic and a second-line therapeutic.
In cases where the sponsor has not collected microarray data, Dynemo can run the microarray gene-expression studies on samples provided by the sponsor in collaboration with one of our CLIA certified reference laboratory partners.
Mechanism of action
Dynemo can analyze microarray data taken before and after therapeutic intervention to determine what effects the drug or drug combination has on the organization of the PPI network. Combined with an understanding of what network organization pattern results in drug-response, this information can assist in understanding the drug’s mechanism of action.
Companion diagnostics
Upon completion of efficacy and/or mechanism of action analysis, Dynemo’s algorithms will be trained to recognize relative gene-expression patterns associated with drug-responsiveness. With this capability, Dynemo will provide companion diagnostics for follow-on clinical studies, or for use of the drug on the market. Using the example of cancer, a tissue sample from biopsy or surgical resection will be collected and shipped to a reference lab for microarray analysis, the microarray data will then be analyzed by Dynemo, which will predict the patient’s responsiveness to the drug or drug combination prior to administration.
Drugs are compounds that interact with biological targets, which are typically key proteins that are involved in specific signaling pathways in the cell. Complex diseases, like cancer and autoimmune disease, are often caused by alterations in multi-protein signaling pathways, so drugs can treat these diseases by correcting the pathways via stimulation or blockage of key proteins. There is an inherent degree of variability in complex diseases, however, and two patients with the same disease may have slightly different alterations in the same signaling pathway – these subtle differences explain the variation in effectiveness of certain drugs between patients.
The ability to observe changes in the organization of the PPI network in, for example, a tumor cell can allow for a better understanding of why a drug might be effective in one patient versus another. Scrutinizing the relative abundance of proteins in the aberrant signaling pathway is a new means to differentiate and predict drug-responsive patients and non-responsive patients.
Clinical trials
Dynemo provides analytical services to improve results from clinical efficacy studies. For studies in which gene-expression microarray data has been collected, the sponsor can upload de-identified raw microarray data (with corresponding drug-response profiles) via a secure web-portal to Dynemo’s servers. Dynemo will then analyze the data and consult the sponsor on the results, which may include: a PPI network organization pattern that corresponds to drug-responsiveness or several patterns that are associated with a varying degree of responsiveness; and detailed information about which protein-protein interactions differ between states.
The benefit to the sponsor is a drug that is highly efficacious in a particular subpopulation, which, for example, could make the difference between a third-line therapeutic and a second-line therapeutic.
In cases where the sponsor has not collected microarray data, Dynemo can run the microarray gene-expression studies on samples provided by the sponsor in collaboration with one of our CLIA certified reference laboratory partners.
Mechanism of action
Dynemo can analyze microarray data taken before and after therapeutic intervention to determine what effects the drug or drug combination has on the organization of the PPI network. Combined with an understanding of what network organization pattern results in drug-response, this information can assist in understanding the drug’s mechanism of action.
Companion diagnostics
Upon completion of efficacy and/or mechanism of action analysis, Dynemo’s algorithms will be trained to recognize relative gene-expression patterns associated with drug-responsiveness. With this capability, Dynemo will provide companion diagnostics for follow-on clinical studies, or for use of the drug on the market. Using the example of cancer, a tissue sample from biopsy or surgical resection will be collected and shipped to a reference lab for microarray analysis, the microarray data will then be analyzed by Dynemo, which will predict the patient’s responsiveness to the drug or drug combination prior to administration.