Biomarkers for response to rapamycin analogs

US10610521B2 · kind B2 · utility

Assignee

• Memorial Sloan Kettering Cancer Center · US

Inventors

• James Hsieh · Ladue, US
• Michael Berger · Wiesbaden, DE
• Robert Motzer · Ridgewood, US
• Martin H. Voss · New York, US
• A Ari Hakimi · New Rochelle, US
• Can Pham · New York, US
• Emily Cheng · Englewood Cliffs, US
• Angela Rose Brannon · Cambridge, US
• Jianing Xu · The Bronx, US

Key dates

• Filing date: Sep 14, 2015
• Grant date: Apr 7, 2020
• Expiry date: Jun 7, 2036

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C12Q2600/156
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

The present invention relates to the use of one or more biomarkers to evaluate the likelihood that a rapamycin analog would produce an anti-cancer effect in a subject. It is based, at least in part, on the results of experiments employing an integrated next-generation sequencing approach to interrogate spatially separated tumor specimens from the same individuals to decipher intra-tumor and intertumor heterogeneity and determine the oncogenomic basis of exceptional therapeutic benefit to rapalogs in kidney cancer patients. These experiments implicated loss of function mutations in TSC1 and/or TSC2 and/or gain-of-function of mTOR in therapeutic responsiveness to rapamycin analogs. Accordingly, in non-limiting embodiments, the present invention provides for assay methods and kits for determining the presence of loss of function mutations in TSC1 and/or TSC2 and/or gain-of-function of mTOR, and methods of using such determinations in selecting a therapeutic regimen for a cancer patient and in methods of treating cancer patients. In particular non-limiting embodiments, a plurality of tumor sites are evaluated and the composite effect of the genetic background on mTOR function is assess…