Individualized cancer treatment
View Patent ↗Methods to formulate treatments for individual cancer patients by assessing genomic and/or phenotypic differences between cancer and normal tissues and integrating the results to identify dysfunctional pathways are described.
1. A method to identify at least one therapeutic target in an individual cancer patient, which method consists essentially of:
(a) assaying multiple characteristics of the genome and/or multiple characteristics of the molecular phenotype in a biopsy of the cancer afflicting said patient to obtain one or more first data sets wherein each data set consists of a single type of characteristic and assaying said characteristics in normal tissue from said individual patient to obtain one or more second data sets, wherein said multiple characteristics represent a sufficient fraction of the networks of interacting genes and their corresponding proteins in any said patient to permit identification of at least one dysregulated pathway;
(b) identifying characteristics from (a) in said one or more first data sets which differ from those in said one or more second data sets to obtain differentiated characteristics; and
(c) matching said differentiated characteristics of (b) to pathways to identify one or more pathways dysregulated in said cancer biopsy as compared to normal tissue for therapeutic intervention wherein
(i) each pathway comprises a multiplicity of interacting proteins curated from the literature;
(ii) the differentiated characteristics are used to identify dysregulated pathways by applying statistical approaches based on triangulation to each pathway as a whole; and
(iii) whereby one or more pathways is determined to be dysregulated in said individual patient's cancer as compared to the patient's normal tissue; and
(d) identifying at least one therapeutic target wherein interaction with said target would overcome dysregulation of said pathway;
wherein step (b) and/or the step (c) is performed by a computer; and
wherein each said identified dysregulated pathway contains a sufficient number of independent data points to overcome statistical limitations of one or two samples and exhibits a coherent pattern whereby gene products are dysregulated in accordance with the pathway itself; and
said target is responsive to approved or investigational drugs or biologics.
2. The method of claim 1 , wherein said pathways in step (c) (i) are curated by accessing at least one database describing pathways exhibited by gene products.
3. The method of claim 1 , wherein said pathways are metabolic pathways and/or signal transduction pathways.
4. The method of claim 1 , wherein characteristics of the genome are selected from the group consisting of single nucleotide polymorphisms (SNPs), copy number variants (CNVs), loss of heterozygosity (LOH), gene methylation, and sequence information.
5. The method of claim 1 , wherein characteristics of the molecular phenotype are selected from the group consisting of overexpression or underexpression of genes, proteomic data, and protein activity data.
6. The method of claim 1 , wherein said triangulating is used to assess validity of the ascertained pathways as compared to noise.
7. The method of claim 1 , wherein said triangulating applies one or more of algorithms 1a, 2a, 3a, 1b, 2b and 3b.
8. The method of claim 1 , wherein at least two datasets which are different with respect to the type of characteristics are obtained from each of said cancer biopsy and normal tissue of said individual patient and said method further includes integrating the identified differentiated characteristics from said at least two datasets to identify patterns that are ascertainable only from concurrent matching of said different characteristics to said pathways.
9. The method of claim 1 , which further includes extrapolating the identified differentiated characteristics to characteristics that have not been measured.
10. The method of claim 1 , which further includes designing a treatment protocol using drugs and/or biologics that interact with said at least one target.
11. The method of claim 10 , which further includes formulating said designed treatment protocol into pharmaceutical compositions.
12. The method of claim 10 , which further includes treating said patient with the designed treatment protocol.
13. The method of claim 10 , which further includes applying the identified differentiated characteristics and treatment protocol design to diagnostic and therapeutic discovery protocols.