Methods and materials for examining pathways associated with glioblastoma progression
AssigneeThe Regents of the University of California
InventorsPaul S. Mischel, Charles L. Sawyers, Bradley L. Smith, Katherine Crosby
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Abstract
The invention disclosed herein provides methods for the examination and/or quantification of biochemical pathways that are disregulated in pathologies such as cancer and to reagents and kits adapted for performing such methods.
Claims24
A method for identifying a mammalian glioma tumor that is likely to respond, or is responsive to an EGFR polypeptide (SEQ ID NO:
- 7) inhibitor or an mTOR polypeptide (SEQ ID NO:
- 2) inhibitor, the method comprising examining a sample obtained from the tumor for:
- (a) the expression of PTEN polypeptide (SEQ ID NO:
- 5);
- and the presence of at least one of,
- (b) phosphorylated S6 ribosomal polypeptide (SEQ ID NO:
- 1);
- (c) EGFR polypeptide (SEQ ID NO:
- 7)
- (d) phosphorylated AKT polypeptide (SEQ ID NO:
- 4);
- and
- (e) phosphorylated ERK polypeptide (SEQ ID NO:
- 8)
- wherein decreased expression of PTEN polypeptide together with decreased phosphorylation of S6 ribosomal polypeptide in the sample, as compared to a control, identifies the glioma tumor as likely to respond or responsive to an mTOR inhibitor, and
- wherein decreased expression an of PTEN together with normal phosphorylation of S6 ribosomal polypeptide in the sample, as compared to a control, identifies the glioma tumor as not likely to respond or unresponsive to an mTOR inhibitor, and
- wherein normal or increased expression of PTEN and increased expression and/or activity of EGFR together with increased phosphorylation of AKT and/or phosphorylation of ERK identifies the glioma tumor as not likely to respond and/or unresponsive to an EGFR inhibitor.
A method for identifying a mammalian glioma tumor that does not express a PTEN polypeptide (SEQ ID NO:
- 5) and which is likely to respond or is responsive to an inhibitor of mTOR polypeptide (SEQ ID NO:
- 2) activity, the method comprising examining a sample obtained from the tumor for the presence of phosphorylated S6 ribosomal polypeptide (SEQ ID NO:
- 1) after contacting the tumor or the sample with the inhibitor,
- wherein, an observable decrease in phosphorylated S6 ribosomal polypeptide in the sample, as compared to a control that is not contacted with the inhibitor identifies the glioma tumor as likely to respond or responsive to the inhibitor, and
- wherein no observable decrease in phosphorylated S6 ribosomal polypeptide in the sample, as compared to a control identifies the glioma tumor as not likely to respond or unresponsive to the inhibitor.
A method for identifying a mammalian glioma tumor that expresses a PTEN polypeptide (SEQ ID NO:
- 5) and which is not likely to respond or is nonresponsive to an inhibitor of EGFR polypeptide (SEQ ID NO:
- 7) activity, the method comprising examining a sample obtained from the tumor for the presence of EGFR (SEQ ID NO:
- 7) and the presence of a phosphorylated AKT polypeptide (SEQ ID NO:
- 4) or the presence of a phosphorylated ERK polypeptide (SEQ ID NO:
- 8), after contacting the tumor or the sample with the inhibitor,
- wherein an increase in the levels of the EGFR polypeptide and the levels of phosphorylated AKT polypeptide or phosphorylated ERK polypeptide identifies the glioma tumor as not likely to respond or nonresponsive to the inhibitor.
A kit for characterizing a mammalian glioma tumor or cell, the kit comprising:
- (a) an antibody that binds PTEN (SEQ ID NO:
- 5);
- and one or more of the following:
- (b) an antibody that binds phosphorylated S6 ribosomal polypeptide (SEQ ID NO:
- 1);
- (c) an antibody that binds EFGR (SEQ ID NO:
- 7);
- (d) an antibody that binds phosphorylated AKT (SEQ ID NO:
- 4);
- and
- (e) an antibody that binds phosphorylated ERK (SEQ ID NO:
- 8).
Dependencies are inferred from the claim text.