Markers of tumor cell response to anti-cancer therapy

Abstract

Compositions and methods for determining circulating biomolecules before, during, and/or after treatment of a patient with an anti-cancer or anti-tumor drug (or putative drug) are described. Methods of treatments based on the compositions and methods described herein are also provided. Noninvasive methods and kits are provided for assessing the efficacy of an anti-cancer therapy for killing or damaging cancer cells. Embodiments are used to determine the cancer-killing efficacy of an anti-cancer drug in a patient, to optimize the selection of an anti-cancer drug for treatment of a patient, to adjust the dosage of an anti-cancer drug for treatment of a particular cancer in a patient and for identifying useful anti-cancer therapeutics for any one particular type of cancer.

1 - 53 . (canceled) 
     
     
         54 . A method of controlling dosage of an anti-tumor drug administered to human patients having a colon cancer, comprising:
 determining a first level of a panel of tumor-responsive biomarkers comprising miR-21-3p, miR-101-5p, miR-122-3p, miR-197-3p, miR-429, miR-501-3p, miR-509-3p, miR-598, miR-206, miR-885-5p, miR-1972, miR-30d-3p, miR-483-5p, and miR-708-3p in first biological samples of the patients, wherein the first samples are obtained before administering to the patients a first dose of an anti-tumor drug;   determining a second level of the panel of tumor-responsive biomarkers in subsequent biological samples of the patients, wherein the subsequent samples are obtained after administering to the patients the first dose of the anti-tumor drug; wherein increases in each of biomarkers miR-30d-3p, miR-483-5p, and miR-708-3p and decreases in each of miR-21-3p, miR-101-5p, miR-122-3p, miR-197-3p, miR-429, miR-501-3p, miR-509-3p, miR-598, miR-206, miR-885-5p, and miR-1972 indicate a favorable response to treatment   thereafter, administering different regimens of the drug to different patients depending on the response to treatment indicated by the biomarkers in the patients.   
     
     
         55 . The method of  claim 54 , further comprising:
 determining the amount of a control marker in the patients before and after administering to the patients the first dose of the anti-tumor drug, wherein the different regimens of the drug administered to the different patients are adjusted according to the change in the level of the tumor-responsive biomarkers in the patients compared to the change in the level of the control marker in the patients in the determining step,   wherein the control marker is different from the tumor-responsive biomarkers.   
     
     
         56 . The method of  claim 54 , wherein the first biological samples and the subsequent biological samples are fluid samples obtained from blood, plasma, serum, cerebrospinal fluid, synovial fluid, lymph, saliva, or urine of the patients. 
     
     
         57 . The method of  claim 54 , wherein the subsequent biological samples are obtained from the patients immediately after, 6 hours after, 12 hours after, 1 day after, 2 days after, 3 days after, 4 days after, 5 days after, 10 days after, two weeks after, one month after, 1-3 months after, 3-6 months after, or 6-12 months after administration of the first dose of the anti-tumor drug. 
     
     
         58 . The method of  claim 54 , wherein the anti-tumor drug is irinotecan. 
     
     
         59 . The method of  claim 54 , wherein the different regimens of the anti-tumor drug administered to the different patients are administered to the different patients along with a different anti-tumor drug. 
     
     
         60 . The method of  claim 54 , wherein the determining of the first level and the second level of the panel of tumor-responsive biomarkers is by microarray analysis.