Methods for determining the prognosis for cancer patients using tucan

• US 7,163,801 B2
• Filed: 05/07/2002
• Issued: 01/16/2007
• Est. Priority Date: 09/01/1999
• Status: Expired due to Fees

• Current Assignee: Burnham Institute For Medical Research
• Original Assignee: The Burnham Institute
• Inventors: Reed, John C.
• Primary Examiner(s): WEHBE, ANNE MARIE SABRINA
• Application Number:
  US10/141,618
• Publication Number:
  US 20030165887A1
• Time in Patent Office: 1,715 Days
• Field of Search: 435/7.1, 435/7.2, 435/7.21, 435/7.23, 435/325
• US Class Current: 435/7.23
• CPC Class Codes: A01K 2217/05 Animals comprising random inserted nucleic acids (transgenic)
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: C07K 14/4747 Apoptosis related proteins
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/118 Prognosis of disease development
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: G01N 2333/96466 Cysteine endopeptidases (3.4.22)
• CPC Class Codes: G01N 2510/00 Detection of programmed cell death, i.e. apoptosis
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 33/57419 of colon
• CPC Class Codes: G01N 33/57484 involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites

Abstract

The invention provides methods for determining a prognosis for survival for a cancer patient. One method involves (a) measuring a level of a TUCAN in a neoplastic cell-containing sample from the cancer patient, and (b) comparing the level of TUCAN in the sample to a reference level of TUCAN, wherein a low level of TUCAN in the sample correlates with increased survival of the patient. Another method involves (a) measuring a level of TUCAN in a neoplastic cell-containing sample from the cancer patient, and (b) classifying the patient as belonging to either a first or second group of patients, wherein the first group of patients having low levels of TUCAN is classified as having an increased likelihood of survival compared to the second group of patients having high levels of TUCAN.

Claims

1. A method for determining the prognosis for survival for a colon cancer patient having stage II colon carcinoma, comprising:

(a) measuring a level of TUCAN polypeptide in a colon cancer cell-containing sample from said colon cancer patient, and

(b) comparing the level of TUCAN polypeptide in said sample to a reference level of TUCAN polypeptide from normal colon tissue, wherein a lower level of TUCAN polypeptide relative to said reference level correlates with increased survival of said patient.

2. The method of claim 1, wherein said survival is overall survival.

3. The method of claim 1, wherein said survival is disease-free survival.

4. The method of claim 1, wherein said sample is colon tumor tissue.

5. The method of claim 1, wherein said sample is a fluid selected from the group consisting of blood, serum, urine, semen and stool.

6. The method of claim 1, wherein a level of said TUCAN polypeptide is measured using an antibody specifically reactive with TUCAN.

7. The method of claim 1, wherein said level of TUCAN polypeptide is used to determine if said patient is at risk for relapse.

8. The method of claim 1, wherein said level of TUCAN polypeptide is used to determine a proper course of treatment for said patient.

9. A method of determining a prognosis for survival for a colon cancer patient having stage II colon carcinoma, comprising:

(a) measuring levels of TUCAN polypeptide and one or more biomarker polypeptides selected from the group consisting of cIAP2, Apaf1, Bcl-2 and Smac in a colon cancer cell-containing sample from said colon cancer patient, and

(b) comparing the level of TUCAN polypeptide and the one or more selected biomarker polypeptides in said sample to a reference level of TUCAN polypeptide and said one or more selected biomarker polypeptides from normal colon tissue, wherein a lower level of TUCAN polypeptide and a higher level of any of Apaf1, Bcl-2, or Smac, or a lower level of TUCAN polypeptide and a lower level of cIAP2 in said sample relative to said reference level correlate with increased survival of said patient.

10. The method of claim 9, wherein said survival is overall survival.

11. The method of claim 9, wherein said survival is disease-free survival.

12. The method of claim 9, wherein cIAP2 is a selected biomarker.

13. The method of claim 9, wherein Apaf1 is a selected biomarker.

14. The method of claim 9, wherein Bcl-2 is a selected biomarker.

15. The method of claim 9 wherein Smac is a selected biomarker.

16. The method of claim 9, wherein said sample is colon tumor tissue.

17. The method of claim 9, wherein said sample is a fluid selected from the group consisting of blood, serum, semen, urine, and stool.

18. The method of claim 9, wherein a level of TUCAN or a biomarker polypeptide is measured using an antibody specifically reactive with TUCAN or the biomarker polypeptide.

19. The method of claim 9, wherein the levels of TUCAN polypeptide and one or more biomarker polypeptide are used to determine if said patient is at risk for relapse.

20. The method of claim 9, wherein the levels of TUCAN polypeptide and one or more biomarker polypeptide are used to determine a proper course of treatment for said patient.

21. The method of claim 9, further comprising selecting two or more biomarkers from the group consisting of cIAP2, Apaf1, Bcl-2 and Smac.

22. A method of determining a prognosis for survival for a colon cancer patient having stage II colon carcinoma, comprising:

(a) measuring a level of TUCAN polypeptide in a colon cancer cell-containing sample from said colon cancer patient;

(b) comparing the level of TUCAN polypeptide in said sample to a reference level of TUCAN polypeptide from normal colon tissue; and

(c) classifying said patient as belonging to either a first or second group of patients, wherein said first group of patients having lower levels of TUCAN polypeptide relative to said reference level is classified as having an increased likelihood of survival compared to said second group of patients having higher levels of TUCAN polypeptide relative to said reference level.

23. The method of claim 22, wherein said survival is overall survival.

24. The method of claim 22, wherein said survival is disease-free survival.

25. The method of claim 22, wherein said sample is colon tumor tissue.

26. The method of claim 22, wherein said sample is a fluid selected from the group consisting of blood, serum, urine, semen and stool.

27. The method of claim 22, wherein a level of a TUCAN polypeptide is measured using an antibody specifically reactive with TUCAN polypeptide.

28. The method of claim 22, further comprising:

(a) determining a level of cIAP2 polypeptide in said colon cancer cell-containing sample from said colon cancer patient,

(b) comparing the level of cIAP2 in said sample to a reference level of cIAP2 from normal colon tissue; and

(c) classifying said patient as belonging to either a first or second group of patients, wherein said first group of patients having lower levels of TUCAN polypeptide and lower levels of cIAP2 polypeptide relative to said reference levels is classified as having increased likelihood of survival compared to said second group of patients having higher levels of TUCAN polypeptide and higher levels of cIAP2 polypeptide relative to said reference levels.

29. The method of claim 22, further comprising:

(a) determining a level of a biomarker polypeptide selected from the group consisting of Apaf1, Smac and Bcl-2 in said colon cancer cell-containing sample from said colon cancer patient,

(b) comparing the level of said biomarker polypeptide in said sample to a reference level of said biomarker polypeptide from normal colon tissue; and

(c) classifying said patient as belonging to either a first or second group of patients, wherein said first group of patients having lower levels of TUCAN polypeptide and higher levels of any of Apaf1, Smac or Bcl-2 polypeptide relative to said reference levels is classified as having increased likelihood of survival compared to said second group of patients having higher levels of TUCAN polypeptide and lower levels of Apaf1, Smac, or Bcl-2 polypeptide relative to said reference levels.

30. The method of claim 29, wherein Apaf1 is a selected biomarker.

31. The method of claim 29, wherein Bcl-2 is a selected biomarker.

32. The method of claim 29, wherein Smac is a selected biomarker.