Resistance biomarkers for HDAC inhibitors

Abstract

Provided herein are methods for identifying a cancer patient at risk for resistance to an HDAC inhibitor therapy, comprising obtaining a tumor sample from the cancer patient; detecting the presence of Testis-specific Y-encoded-like protein 5 (TSPYL5) expression in the sample; quantifying a level of the TSPYL5 expression in the sample, wherein a high level of the TSPYL5 expression, relative to a defined expression threshold of the TSPYL5, correlates with resistance to the HDAC inhibitor therapy; and applying the correlation to identify the cancer patient at risk for resistance to the HDAC inhibitor therapy. Also provided is a method for identifying a cancer patient with an increased likelihood of a positive clinical response to an HDAC inhibitor therapy comprising obtaining a tumor sample from the cancer patient; detecting the presence of Testis-specific Y-encoded-like protein 5 (TSPYL5) expression in said sample; quantifying a level of said TSPYL5 expression in said sample, wherein a low level of the TSPYL5 expression, relative to a defined expression threshold of the TSPYL5, identifies said cancer patient with an increased likelihood of a positive clinical response to said HDAC inhibitor therapy. Related methods and compositions are also provided.

Description

RELATED APPLICATIONS[0001]This application claims priority to U.S. provisional application Ser. No. 61 / 698,341, filed Sep. 7, 2012; U.S. provisional application Ser. No. 61 / 726,464, filed Nov. 14, 2012; and U.S. provisional application Ser. No. 61 / 784,501, filed Mar. 14, 2013, which are incorporated herein by reference in their entireties.[0002]The invention relates generally to the field of personalized medicine and, more specifically to the discovery that TSPYL5, encoding testis-specific Y-like protein, serves as a tumor biomarker for resistance to cancer treatment with a histone deacetylase (HDAC) inhibitor.BACKGROUND[0003]Cancer is a major public health problem in the United States and in the world. Currently, one in 4 deaths in the United States is due to cancer. Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths expected in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and surviv...

AI Technical Summary

Benefits of technology

The patent provides a method for identifying cancer patients who may not respond to treatment with an HDAC inhibitor therapy. This method involves detecting the presence of a specific protein (TSPYL5) in a tumor sample from the cancer patient and measuring its level of expression. A high level of TSPYL5 expression indicates resistance to HDAC inhibitor therapy, while a low level indicates an increased likelihood of a positive clinical response. Communication of the identification of the cancer patient to a health care provider can help select or deselect the patient for HDAC inhibitor therapy. The patent also provides a therapeutically effective amount of the HDAC inhibitor for the selected patient and initiates HDAC inhibitor therapy using any of a group of HDAC inhibitors, such as romidepsin, panobinostat, vorinostat, and entinostat. Kits containing HDAC inhibitors and reagents for detecting TSPYL5 expression in a tumor sample are also provided.

Problems solved by technology

Cancer is a major public health problem in the United States and in the world.

However, the validity of these markers is likely to be limited to these specific studies.

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