# US 2016/0258024 A1 · Compositions and methods for identification of relapse risk and treatment in patients with colorectal cancer > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2016/0258024 A1 - Document ID: US20160258024A1 - Status: Published application - Kind: A1 - Application number: 15/027,284 - Filed: 2014-10-07 - Published: 2016-09-08 - Earliest claimed: 2013-10-07 - Assignees: Georgetown University - Applicants: Georgetown University - Inventors: Anton Wellstein; Narayan Shivapurkar - Web page: https://patentgrep.com/patent/US20160258024A1 ## CPC - C12Q 1/6886: for cancer (immunoassay for cancer G01N33/575) - C12Q 2600/106: Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism - C12Q 2600/118: Prognosis of disease development - C12Q 2600/178: miRNA, siRNA or ncRNA - C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES ## Abstract In certain aspects, the disclosure relates to methods of predicting recurrence of colorectal cancer by using a combination of microRNAs in the circulation, wherein the microRNAs are selected from the group consisting of miR-15a, miR-103, miR-148a, miR-320a, miR-451 and miR-596. In other aspects, the disclosure relates to methods of treating colorectal cancer by administering a therapeutic agent after determining an increased risk of recurrence. ## Claims ### Claim 1 A method for predicting recurrence of early stage colorectal cancer in a patient, comprising: a) providing a biological material comprising circulating microRNAs from a patient diagnosed with stage 0, stage I or stage II colorectal cancer, b) measuring in the biological material the levels of two or more microRNAs selected from: miR-15a, miR-103, miR-148a, miR-320a, miR-451 and miR-596, and c) evaluating the measured levels; wherein the measured levels are indicative of a risk of recurrence of the cancer. ### Claim 2 A method for predicting recurrence of early stage colorectal cancer in a patient, comprising: a) providing a biological material comprising circulating microRNAs from a patient diagnosed with stage 0, stage I or stage II colorectal cancer, b) requesting a test comprising measuring in the biological material the levels of two or more microRNAs selected from: miR-15a, miR-103, miR-148a, miR-320a, miR-451 and miR-596, and c) evaluating the measured levels; wherein the measured levels are indicative of a risk of recurrence of the cancer. ### Claim 3 A method for determining a treatment regimen for a patient diagnosed with early stage colorectal cancer, comprising: a) providing a biological material comprising circulating microRNAs from a patient diagnosed with stage 0, stage I or stage II colorectal cancer, b) measuring in the biological material the levels of two or more microRNAs selected from: miR-15a, miR-103, miR-148a, miR-320a, miR-451 and miR-596, c) evaluating the measured levels, and d) providing additional cancer therapy, after surgical resection of the colorectal cancer, to the patient if the measured levels are indicative of a high risk of recurrence of the cancer. ### Claim 4 A method for determining a treatment regimen for a patient diagnosed with early stage colorectal cancer, comprising: a) providing a biological material comprising circulating microRNAs from a patient diagnosed with stage 0, stage I or stage II colorectal cancer, b) requesting a test comprising measuring in the biological material the levels of two or more microRNAs selected from: miR-15a, miR-103, miR-148a, miR-320a, miR-451 and miR-596, c) evaluating the measured levels; and d) providing additional cancer therapy, after surgical resection of the colorectal cancer, to the patient if the measured levels are indicative of a high risk of recurrence of the cancer. ### Claim 5 A method for treating early stage colorectal cancer in a patient in need thereof, comprising: a) providing a biological material comprising circulating microRNAs from a patient diagnosed with stage 0, stage I or stage II colorectal cancer, b) measuring in the biological material the levels of two or more microRNAs selected from: miR-15a, miR-103, miR-148a, miR-320a, miR-451 and miR-596, c) evaluating whether the patient is at risk of recurrence of the cancer based on the levels of the microRNAs in the biological material, and d) if the measured levels of the microRNAs in the biological material are indicative of a high risk of recurrence, (i) monitor the patient at more frequent intervals or using tests that exceed the standard of care, and/or (ii) provide additional treatment that exceeds the standard of care. ### Claim 6 A method for treating early stage colorectal cancer in a patient in need thereof, comprising: a) providing a biological material comprising circulating microRNAs from a patient diagnosed with stage 0, stage I or stage II colorectal cancer, b) requesting a test comprising measuring in the biological material the levels of two or more microRNAs selected from: miR-15a, miR-103, miR-148a, miR-320a, miR-451 and miR-596, c) evaluating whether the patient is at risk of recurrence of the cancer based on the levels of the microRNAs in the biological material, and d) if the measured levels of the microRNAs in the biological material are indicative of a high risk of recurrence, (i) monitor the patient at more frequent intervals or using tests that exceed the standard of care, and/or (ii) provide additional treatment that exceeds the standard of care. ### Claim 7 (depends on 1, 2, 3, 4, 5, 6) The method of any of claims 1-6, wherein the two or more microRNAs comprise one of miR-103 or miR-596. ### Claim 8 (depends on 1, 2, 3, 4, 5, 6) The method of any of claims 1-6, wherein the two or more microRNAs comprise miR-103 and miR-596. ### Claim 9 (depends on 1, 2, 3, 4, 5, 6) The method of any of claims 1-6, wherein the two or more microRNAs consist of miR-103 and miR-596. ### Claim 10 (depends on 1, 2, 3, 4, 5, 6) The method of any of claims 1-6, wherein measuring in the biological material the levels of two or more microRNAs comprises measuring the levels of miR-15a, miR-103, miR-148a, miR-320a, miR-451 and miR-596. ### Claim 11 (depends on 1, 2, 3, 4, 5, 6) The method of any of claims 1-6, wherein measuring in the biological material the levels of two or more microRNAs consists of measuring the levels of miR-15a, miR-103, miR-148a, miR-320a, miR-451 and miR-596. ### Claim 12 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11) The method of any of claims 1-11, wherein the biological material is a biological fluid. ### Claim 13 (depends on 12) The method of claim 12, wherein the biological fluid is selected from: blood plasma, blood serum, whole blood, urine, or feces. ### Claim 14 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13) The method of any of claims 1-13, wherein the biological material is obtained before the cancer is initially surgically resected. ### Claim 15 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13) The method of any of claims 1-13, wherein the biological material is obtained after recovery from surgical resection of the cancer. ### Claim 16 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15) The method of any of claims 1-15, wherein steps (a) and (b) are repeated periodically if the measured levels are indicative of a low risk of recurrence of the cancer. ### Claim 17 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16) The method of any of claims 1-16, wherein the microRNA levels are measured using quantitative RT-PCR. ### Claim 18 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16) The method of any of claims 1-16, wherein the microRNA levels are measured using hybridization methods. ### Claim 19 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16) The method of any of claims 1-16, wherein the microRNA levels are measured using an array. ### Claim 20 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19) The method of any of claims 1-19, wherein the microRNA levels are normalized to a control. ### Claim 21 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20) The method of any of claims 1-20, wherein the risk of recurrence of the cancer is determined by comparing the microRNA levels to a reference gene signature. ### Claim 22 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20) The method of any of claims 1-20, wherein the risk of recurrence of the cancer is determined by hierarchical clustering of the microRNA levels of the biological material with microRNA levels of the control biological materials from colorectal cancer patients with known recurrence outcome. ### Claim 23 (depends on 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22) The method of any of claims 3-22, wherein the additional therapy comprises chemotherapy, radiation therapy, or therapy targeted to specific pathways known to be important in colorectal cancer or the immune system. ### Claim 24 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23) The method of any of claims 1-23, wherein the risk of recurrence of the cancer is predicted with at least 75% likelihood. ### Claim 25 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23) The method of any of claims 1-23, wherein the risk of recurrence of the cancer is predicted with at least 90% likelihood. ### Claim 26 A kit for measuring the levels of two or more microRNAs selected from: miR-15a, miR-103, miR-148a, miR-320a, miR-451 and miR-596, comprising reagents for specifically measuring the levels of the selected microRNAs. ### Claim 27 (depends on 26) The kit of claim 26, wherein the two or more microRNAs comprise one of miR-103 or miR-596. ### Claim 28 (depends on 26) The kit of claim 26, wherein the two or more microRNAs comprise miR-103 and miR-596. ### Claim 29 (depends on 26) The kit of claim 26, wherein the two or more microRNAs consist of miR-103 and miR-596. ### Claim 30 (depends on 26) The kit of claim 26, wherein the kit comprises reagents for specifically measuring the levels of miR-15a, miR-103, miR-148a, miR-320a, miR-451 and miR-596. ### Claim 31 (depends on 26) The kit of claim 26, wherein the kit comprises reagents for specifically measuring the levels of two or more microRNAs, and wherein the microRNAs consist of miR-15a, miR-103, miR-148a, miR-320a, miR-451 and miR-596. ### Claim 32 (depends on 26, 27, 28, 29, 30, 31) The kit of any of claims 26-31, wherein the reagents are for measuring microRNA levels using quantitative RT-PCR. ### Claim 33 (depends on 26, 27, 28, 29, 30, 31) The kit of any of claims 26-31, wherein the reagents are for measuring microRNA levels using hybridization methods. ### Claim 34 (depends on 26, 27, 28, 29, 30, 31) The kit of any of claims 26-31, wherein the reagents comprise reagents for measuring microRNA levels using an array. ### Claim 35 (depends on 26, 27, 28, 29, 30, 31, 32, 33, 34) The kit of any of claims 26-34, wherein the microRNA levels are normalized to a control. ### Claim 36 (depends on 26, 27, 28, 29, 30, 31, 32, 33, 34, 35) The kit of any of claims 26-35, wherein the levels of the selected microRNAs predict the risk of recurrence of the cancer. ### Claim 37 (depends on 36) The kit of claim 36, wherein the risk of recurrence of the cancer is determined by comparing the microRNA levels to a gene signature. ### Claim 38 (depends on 36) The kit of claim 36, wherein the risk of recurrence of the cancer is determined by hierarchical clustering of the biological material with control biological materials from colorectal cancer patients with known recurrence outcome. ### Claim 39 (depends on 36, 37, 38) The kit of any of claims 36-38, wherein the risk of recurrence of the cancer is predicted with at least 75% likelihood. ### Claim 40 (depends on 36, 37, 38) The kit of any of claims 36-38, wherein the risk of recurrence of the cancer is predicted with at least 90% likelihood.