| 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. |
| 主权项 |
1. A method of producing an anti-cancer effect in a cancer, comprising determining whether cells of the cancer contain a biomarker selected from a TSC1 biomarker, a TSC2 biomarker, a mTOR biomarker, and a combination thereof, where the cancer is renal cell carcinoma, supependymal giant cell astrocytoma, hormone-receptor positive, HER-2 negative breast cancer, progressive neuroendocrine tumor of pancreatic origin, Hodgkin's lymphoma, non-Hodgkin's lymphoma, endometrial cancer, mantle-cell lymphoma, or melanoma, and, where a TSC1 biomarker, a TSC2 biomarker, and/or a mTOR biomarker is present, administering a therapeutically effective amount of a rapamycin analog to produce an anti-cancer effect. |
