BIOMARKERS OF MIR-34 ACTIVITY

摘要

This invention is based in part on the discovery that miR-34 is independent of p53. It has been discovered that miR-34 functions in a TP53-independent tumor suppression pathway. Specifically, miR-34-induced inhibition of cancer cell growth was found to be the same in p53-normal and p53-deficient cells. Thus, miR-34 has a more central role during tumor suppression that is uncoupled from p53. In the absence of p53, miR-34, unlike certain other miRNAs, is sufficient to induce an up-regulation of genes known to be regulated by p53, including but not limited to p21CIP1/WAF1 (CDKN1A), PUMA, BAX, NOXA, PHLDA3, and MDM2 and a down-regulation of HDAC1. Therefore, these biomarkers can be used as biomarkers of miR-34 activity. The invention is further based on the discovery that some of these biomarkers are indispensable for a therapeutic response to miR-34 activity, and are thus prerequisite biomarkers of miR-34 activity.

主权项

1. A method of treating a subject having cancer, the method comprising:
(a) screening the subject for the presence or absence of at least one prerequisite biomarker for miR-34 activity; (b) administering a miR-34 therapeutic to the subject if the prerequisite biomarker(s) for miR-34 activity is determined to be present; and (c) administering an alternative therapy to the subject if the prerequisite biomarker(s) for miR-34 activity is determined to be absent, thereby treating the subject.