James J. Hsieh,Michael Berger,Robert Motzer,Martin H. Voss,Ari A. Hakimi,Can Pham,Emily Cheng,Rose Brannon,Jianing Xu
申请号：
US14853468
公开号：
US20160067229A1
申请日:
2015.09.14
申请国别(地区):
US
年份:
2016
代理人:
摘要：
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.
