Emily Y Cheng

US Patent:

20160067229, Mar 10, 2016

Filed:

Sep 14, 2015

Appl. No.:

14/853468

Inventors:

- New York NY, US
Michael Berger - New York NY, US
Robert Motzer - Ridgewood NJ, US
Martin H. Voss - New York NY, US
Ari A. Hakimi - New Rochelle NY, US
Can Pham - New York NY, US
Emily Cheng - Englewood Cliffs NJ, US
Rose Brannon - Cambridge MA, US
Jianing Xu - Bronx NY, US

International Classification:

A61K 31/436
C12Q 1/68

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 assessed.