Methods and compositions for determining risk of treatment toxicity
AssigneeThe Board of Trustees of the Leland Stanford Junior University
InventorsGilbert Chu, Virginia G. Tusher, Jean Tang, Kerri Elyse Rieger, Wan-Jen Hong, Robert Tibshirani
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Abstract
Methods are provided for determining whether a patient treated with an anti-proliferative agent is susceptible to toxicity. In practicing the subject methods, an expression profile for the transcriptional response to a therapy is obtained from the patient and compared to a reference profile to determine whether the patient is susceptible to toxicity. In addition, reagents and kits thereof that find use in practicing the subject methods are provided.
Claims12
A method of determining the suitability of a patient for radiation therapy, the method comprising:
- predicting whether a subject will be susceptible to undesirable toxicity resulting from treatment with radiation therapy, said method comprising:
- (a) obtaining transcriptional expression profile for the response to radiation for a sample from said subject from a set of sequences comprising:
- Cyclin B, ATP synthase, CDC28, protein kinase 2, forming-binding protein 17, ribosomal protein 17, ribosomal protein S9, phorbolin-like protein MDS019, tumor necrosis factor superfamily member 7, RNA helicase disrupter of silencing 10, heat shock 27 kD protein 1
- (b) comparing said obtained expression profile to a reference expression profile from a cell known to have a susceptible phenotype for radiation toxicity to determine the probability that said patient is susceptible to undesirable radiation toxicity;
- wherein a patient that is predicted to have a high probability of undesirable radiation toxicity is less suitable for radiation therapy.
A method of optimizing radiation therapy for a patient, the method comprising:
- (a) obtaining transcriptional expression profile for the response to radiation for a sample from said subject from a set of sequences comprising:
- Cyclin B, ATP synthase, CDC28, protein kinase 2, forming-binding protein 17, ribosomal protein 17, ribosomal protein S9, phorbolin-like protein MDS019, tumor necrosis factor superfamily member 7, RNA helicase disrupter of silencing 10, heat shock 27 kD protein 1;
- and
- (b) comparing said obtained expression profile to a reference expression profile from a cell known to have a susceptible phenotype for toxicity from the anti-proliferative therapy to determine the probability that said patient is susceptible to undesirable toxicity;
- wherein a dose of said anti-proliferative therapy is selected to minimize to undesirable toxicity, while providing for effective anti-proliferative activity.
A method of obtaining an expression profile for the transcriptional response to radiation, the method comprising:
- exposing a cell sample from an individual to radiation;
- extracting mRNA from said cell;
- quantitating the level of mRNA from a set of sequences comprising:
- Cyclin B, ATP synthase, CDC28, protein kinase 2, forming-binding protein 17, ribosomal protein 17, ribosomal protein S9, phorbolin-like protein MDS019, tumor necrosis factor superfamily member 7, RNA helicase disrupter of silencing 10, heat shock 27 kD protein 1;
- and
- comparing said level of mRNA to the level of said mRNA present in a cell sample from said individual not exposed to radiation, wherein said comparing step comprises a nearest shrunken centroid analysis step.
Dependencies are inferred from the claim text.