Gene and protein expression profiles associated with the therapeutic efficacy of irinotecan
View Patent ↗The present invention includes gene and protein expression profiles indicative of whether a cancer patient is likely to respond to treatment with irinotecan. By identifying such responsiveness, a treatment provider may determine in advance those patients who would benefit from such treatment, as well as identify alternative therapies for non-responders. The present invention further provide methods of using the gene and/or protein expression profiles and assays for identifying the presence of a gene and/or protein expression profile in a patient sample.
1. A method of determining if a patient diagnosed with colon cancer is a responder to treatment with irinotecan comprising:
a. obtaining colon cancer tissue or cells from the patient diagnosed with colon cancer
b. determining the level of expression in the tissue or cells of: ERBB2 comprising the amino acid sequence of SEQ ID NO. 23, GRB7 comprising the amino acid sequence of SEO ID NO. 24, JNK1 kinase comprising the amino acid sequence of SEQ ID NO. 26, BCL2 comprising the amino acid sequence of SEQ ID NO. 27, MK167 comprising the amino acid sequence of SEQ ID NO. 33, phospho-Akt comprising the amino acid sequence of SEQ ID NO. 35, CD68 comprising the amino acid sequence of SEQ ID NO. 36, BAG1 comprising the amino acid sequence of SEO ID NO. 37, Erk1 kinase comprising the amino acid sequence of SEQ ID NO. 25, phospho-GSK-3-beta comprising the amino acid sequence of SEQ ID NO. 28, MMP11 comprising the amino acid sequence of SEQ ID NO. 29, CTSL2 comprising the amino acid sequence of SEQ ID NO. 30, CCNB1 comprising the amino acid sequence of SEQ ID NO. 31, BIRC5 comprising the amino acid sequence of SEQ ID NO. 32, STK6 comprising the amino acid sequence of SEQ ID NO. 34, MRP14 comprising the amino acid sequence of SEQ ID NO. 44 and GSTM1 comprising the amino acid sequence of SEQ ID NO. 38; and
c. determining that the patient is a responder to treatment with irinotecan if the level of said ERBB2, said GRB7, said JNK1 kinase, said BCL2, said MK167, said phospho-Akt, said CD68 and said BAG1 is elevated in the tissue or cells as compared to the corresponding level of said ERBB2, said GRB7, said JNK1 kinase, said BCL2, said MK167, said phospho-Akt, said CD68 and said BAG1 in normal colon tissue or cells and the level of said Erk1 kinase, said phospho-GSK-3-beta, said MMP11, said CTSL2, said CCNB1, said BIRC5, said STK6, said MRP14 and said GSTM1 is lower in the tissue or cells as compared to the corresponding level of expression of said Erk1 kinase, said phospho-GSK-3-beta, said MMP11, said CTSL2, said CCNB1, said BIRC5, said STK6, said MRP14 and said GSTM1 in normal colon tissue or cells.
2. The method of claim 1 further comprising determining the level of expression of at least one reference protein in said colon cancer tissue or cells and in said normal colon tissue or cells, wherein the reference protein is ACTB comprising the amino acid sequence of SEQ ID NO. 39.
3. The method of claim 2 comprising determining the level of expression of at least one additional reference protein in said colon cancer tissue or cells and in said normal colon tissue or cells selected from the group consisting of: GAPD comprising the amino acid sequence of SEQ ID NO:40, GUSB comprising the amino acid sequence of SEQ ID NO:41, RPLP0 comprising the amino acid sequence of SEQ ID NO:42 and TFRC comprising the amino acid sequence of SEQ ID NO:43.
4. The method of claim 1 wherein step (b) is performed using immunohistochemistry.