Baylor Research Institute

Johns Hopkins University

Cancer Diagnostics Research Innovation

Ajay Goel

C Richard Boland

Yuji Toiyama

Keun Hur

Yoshinaga Okugawa

Stephen J Meltzer

Shusuke Toden

Takatoshi Matsuyama

Clement Boland

Alexander Link

Francesc Balaguer

Jinsei Miyoshi

Raju Kandimalla

Yuriko Mori

Lucia Perez-Carbonell

Roshni Roy

Kunitoshi Shigeyasu

Tsuyoshi Ozawa

Wenhao Weng

Richard C Boland

Dysregulated expression of microRNAs (miRNAs) has emerged as a hallmark feature in human cancers. Aspects of the disclosure relate to methods for selecting optimal therapy for a patient from several alternative treatment options. A major clinical challenge in cancer treatment is to identify the subset of patients who will benefit from a therapeutic regimen, both in metastatic and adjuvant settings. The number of anti-cancer drugs and multi-drug combinations has increased substantially in the past decade, however, treatments continue to be applied empirically using a trial-and-error approach. Here methods and compositions are provided to determine the optimal treatment option for cancer patients.

Methods for diagnosing, prognosing, and treating colorectal cancer using biomarker expression

The current disclosure relates to therapeutic treatments and diagnostic methods for esophageal cancer based on the expression level of biomarker miRNAs. Aspects of the disclosure relate to a method of treating esophageal cancer (EC) in a patient, said method comprising: diagnosing the patient with esophageal cancer when the patient is determined to have an elevated or decreased level of expression of one or more miRNAs selected from mir-15b, miR-17, mir-18a, mir-21, mir-23a, mir-24-2, mir-25, mir-27a, mir-93, mir-103, mir-106b, mir-129-2, mir-139, mir-146b, mir-148a, mir-151, miR-155, mir-181a-1, mir-181a, mir-181b-1, mir-181b, mir-182, mir-183, mir-192, mir-194-1, mir-194-2, mir-196a-1, mir-196a-2, mir-196b, mir-205, mir-215, mir-223, mir-224, mir-335, mir-338, mir-375, mir-421, mir-484, mir-505, mir-769, mir-944, mir-1468, mir-3648, and let-7i in a sample from a patient relative to the expression level of the one or more miRNAs in a control sample; and administering an effective amount of an esophageal treatment to the diagnosed patient.

Methods for diagnosing and treating esophageal cancer

Certain embodiments provide methods and compositions related to clinical management of cancer patients based on the expression level of TMCO3. Further embodiments involve methods and compositions related to treatment of cancer patients or patients determined to have an increased TMCO3 level relative to a control or a reference level that is normal or indicating favorable prognosis.

Methods and compositions involving transmembrane and coiled-coil domains 3 (TM-CO3) in cancer

The present invention includes methods and biomarkers for diagnosing or detecting colorectal cancer metastasis in a human subject by comparing the Alu repeat methylation level in the biological sample to an Alu repeat methylation control level from a normal non-cancerous sample from the human subject, wherein a decrease in the Alu repeat methylation level is indicative of colorectal cancer and colorectal cancer metastasis. The invention also includes methods and biomarkers for diagnosing or detecting colorectal cancer (CRC) metastasis in a human subject by determining a level of expression of let-7i, miR-10b, miR-320a, and miR-221 in the sample from the one or more biological samples; and comparing the level of expression of let-7i, miR-10b, miR-320a, and miR-221 in the sample with the level of expression of let-7i, miR-10b, miR-320a, and miR-221 from normal colorectal tissue, wherein high expression of at least on of let-7i or miR-320a is indicative of a good prognosis for the CRC, while the low expression of at least one of miR-10b or miR-221 is indicative of a good prognosis for the CRC or CRC metastasis.

Identification of metastasis-specific miRNA and hypomethylation signatures in human colorectal cancer

Embodiments provide methods and compositions related to determining treatments for colorectal cancer patients by detection and analysis of the expression level of miRNA such as miR-320e in the patients. Embodiments provide predictive, prognostic and/or diagnostics methods by identifying miRNAs that are useful for clinical management of cancer patients, particularly colorectal cancer patients or patients at risk or determined to have colorectal cancer. Methods and compositions are based, in part, on the discovery that expression of certain miRNAs in cancer patients is associated with advancing cancer stages and/or can predict the responsiveness of cancer therapy, and can, therefore, provide basis for designing treatment strategies. In particular embodiments, the miRNA molecule is miR-320, particularly miR-320e.

MiR-320e and colorectal cancer

Embodiments provide methods and compositions related to detecting neoplasia in ulcerative colitis patients by detection and analysis of the methylation state of miR-1, -9, -124, miR-137 and/or miR-34b/c in samples from UC patients.

Ulcerative colitis (UC)-associated colorectal neoplasia markers

The present invention relates to the field of cancer. More specifically, the present invention relates to the use of biomarkers to detect colorectal cancer. In one aspect, the present invention provides methods for qualifying colorectal cancer status including, but not limited to, diagnosis, prognosis, and risk stratification, in patients. In one embodiment, a method for diagnosing colorectal cancer (CRC) in a patient comprises the steps of (a) collecting a sample from the patient; (b) measuring the methylation levels of one or more biomarkers in the sample collected from the patient; and (c) comparing the methylation levels of the one or more biomarkers with predefined methylation levels of the same biomarkers that correlate to a patient having CRC and predefined methylation levels of the same biomarkers that correlate to a patient not having CRC, wherein a correlation to one of the predefined methylation levels provides the diagnosis.

DNA hypermethylation diagnostic biomarkers for colorectal cancer

Methods and compositions for the diagnosis, prognosis and classification of cancer, especially colorectal cancer, are provided. For example, in certain aspects methods for cancer prognosis using expression or methylation analysis of selected biomarkers are described. Particular aspects of the present invention may include methods and biomarkers for diagnosing or detecting colorectal cancer or metastasis in a subject by measuring a level of expression of biomarker miRNA such as miR-885-5p in the sample from the subject and evaluating the risk of developing cancer or metastasis in the subject.

Tissue and blood-based miRNA biomarkers for the diagnosis, prognosis and metastasis-predictive potential in colorectal cancer

A simple, rapid, inexpensive, and promising commercial biomarker assay method for multiple diseases is described herein. The present invention detects miRNA-based biomarkers in human stool specimens. The method of the present invention amplifies miRNA directly from stool specimens without any prior miRNA extraction. Differential expression of specific microRNAs in stool of colorectal cancer CRC and adenoma patients suggest fecal microRNAs as a novel potential biomarker for colorectal neoplasia detection. The method of the present invention has diagnostic, prognostic, and therapeutic relevance for gastroenterological cancers/colorectal cancer and as well as further acquired or hereditary GI diseases.

Growing community of inventors

Dallas, TX, United States of America

Ajay Goel