Assessment of cellular signaling pathway activity using linear combination(s) of target gene expressions

A method for correcting abnormal activity of a cellular signaling pathway in a subject diagnosed with cancer, wherein the cellular signaling pathway comprises a Wnt pathway, an ER pathway, an AR pathway, or an HH pathway, the method comprising:

• obtaining, by using at least one of Polymerase Chain Reaction (PCR), a microarray technique, and RNA-sequencing, expression levels of three or more target genes of the cellular signaling pathway derived from a sample extracted from the subject;
• determining, by a digital processing device using a mathematical model of the cellular signaling pathway, activity of the cellular signaling pathway in a tissue and/or cells of the subject based at least on the expression levels of the three or more target genes of the cellular signaling pathway measured in an extracted sample of the tissue and/or cells of the subject, wherein the determining comprises/:
• determining a level of a transcription factor (TF) element in the extracted sample of the tissue and/or cells of the subject, the TF element controlling transcription of the three or more target genes of the cellular signaling pathway, the determining being based at least in part on evaluating the mathematical model relating expression levels of the three or more target genes of the cellular signaling pathway to the level of the TF element, the model being based at least in part on one or more linear combination(s) of expression levels of the three or more target genes;
• and
• determining the activity of the cellular signaling pathway in the tissue and/or cells of the subject based on the determined level of the TF element in the extracted sample of the tissue and/or cells of the subject;
• and
• determining that the cellular signaling pathway is operating abnormally in the subject based on the determined activity of the cellular signaling pathway, wherein the determined abnormal operation of the cellular signaling pathway is inactive or underactive operation of the cellular signaling pathway;
• and
• selecting, based on the determined abnormal operation of the cellular signaling pathway, a specific treatment configured to remedy the determined abnormal operation of the cellular signaling pathway, wherein the specific treatment is a signaling pathway upregulator configured to upregulate the operation of the cellular signaling pathway;
• and
• administering, in response to the determined abnormal operation of the cellular signaling pathway and the selection of the specific treatment configured to remedy the determined abnormal operation of the cellular signaling pathway, the signaling pathway upregulator;
• wherein the signaling pathway upregulator is a Wnt pathway upregulator when the determined abnormal operation of the cellular signaling pathway is abnormal operation of the Wnt pathway, wherein the signaling pathway upregulator is an ER pathway upregulator when the determined abnormal operation of the cellular signaling pathway is abnormal operation of the ER pathway, wherein the signaling pathway upregulator is an AR pathway upregulator when the determined abnormal operation of the cellular signaling pathway is abnormal operation of the AR pathway, and wherein the signaling pathway upregulator is an HH pathway upregulator when the determined abnormal operation of the cellular signaling pathway is abnormal operation of the HH pathway.

A method for treating a subject diagnosed with cancer, comprising:

• selecting, based on a determined abnormal operation of a cellular signaling pathway, a specific treatment configured to remedy the determined abnormal operation of the cellular signaling pathway, wherein the specific treatment is a signaling pathway inhibitor configured to inhibit the operation of the cellular signaling pathway, and wherein the cellular signaling pathway comprises a Wnt pathway, an ER pathway, an AR pathway, or an HH pathway, wherein the abnormal operation of a cellular signaling pathway is determined by:
• obtaining, by using at least one of Polymerase Chain Reaction (PCR), a microarray technique, and RNA-sequencing, expression levels of three or more target genes of the cellular signaling pathway derived from a sample extracted from the subject;
• determining, by a digital processing device using a mathematical model of the cellular signaling pathway, activity of the cellular signaling pathway in a tissue and/or cells of the subject based at least on the expression levels of the three or more target genes of the cellular signaling pathway measured in an extracted sample of the tissue and/or cells of the subject, wherein the determining comprises:
• determining a level of a transcription factor (TF) element in the extracted sample of the tissue and/or cells of the subject, the TF element controlling transcription of the three or more target genes of the cellular signaling pathway, the determining being based at least in part on evaluating the mathematical model relating expression levels of the three or more target genes of the cellular signaling pathway to the level of the TF element, the model being based at least in part on one or more linear combination(s) of expression levels of the three or more target genes;
• and
• determining the activity of the cellular signaling pathway in the tissue and/or cells of the subject based on the determined level of the TF element in the extracted sample of the tissue and/or cells of the subject;
• and
• determining that the cellular signaling pathway is operating abnormally in the subject based on the determined activity of the cellular signaling pathway, wherein the determined abnormal operation of the cellular signaling pathway is overactive operation of the cellular signaling pathway;
• and
• administering the signaling pathway inhibitor;
• wherein the signaling pathway inhibitor is a Wnt pathway inhibitor when the determined abnormal operation of the cellular signaling pathway is abnormal operation of the Wnt pathway, wherein the signaling pathway inhibitor is an ER pathway inhibitor when the determined abnormal operation of the cellular signaling pathway is abnormal operation of the ER pathway, wherein the signaling pathway inhibitor is an AR pathway inhibitor when the determined abnormal operation of the cellular signaling pathway is abnormal operation of the AR pathway, and wherein the signaling pathway inhibitor is an HH pathway inhibitor when the determined abnormal operation of the cellular signaling pathway is abnormal operation of the HH pathway.