Cancer comprehensive method for identifying cancer protein patterns and determination of cancer treatment strategies

• US 20040137539A1
• Filed: 01/10/2003
• Published: 07/15/2004
• Est. Priority Date: 01/10/2003
• Status: Abandoned Application

• Current Assignee: ORT, Inc.
• Original Assignee: ORT, Inc.
• Inventors: Bradford, Sherry A.
• Application Number:
  US10/340,858
• Publication Number:
  US 20040137539A1
• Time in Patent Office: Days
• US Class Current: 435/7.23
• CPC Class Codes: G01N 2500/00 Screening for compounds of potential therapeutic value
• 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

A cancer therapy comprehensive method for characterizing a cancer tumor for medical diagnosis and treatment. The method facilitates determination of a cancer protein pattern based on detected nonbasal levels of biomolecular markers (BMMs) associated with a patient'"'"'s tumor. A cancer therapy regimen is selected based on the cancer protein pattern for eradicating the tumor.

Claims

1. A method for characterizing a cancer tumor for medical diagnosis and treatment, comprising:

determining a cancer protein pattern based on detected nonbasal levels of biomolecular markers (BMMs) associated with a patient'"'"'s tumor; and

selecting a cancer therapy regimen based on said cancer protein pattern for eradicating the tumor.

2. A method in accordance with claim 1 wherein said cancer therapy regimen is a first line therapy.

3. A method in accordance with claim 1 wherein said cancer therapy regimen is customized to target cells that express BMMs in said cancer protein pattern above or below basal levels.

4. A method in accordance with claim 1 wherein said BMMs include proteins that can be modulated by protein modulating drugs and said cancer therapy regimen includes protein modulating drugs corresponding to one or more of said BMMs.

5. A method in accordance with claim 4 wherein said protein modulating drugs are selectively combined into a chemo-suite that directly corresponds to said BMM pattern.

6. A method in accordance with claim 1 wherein said BMMs include Class I BMMs representing either tumor promoting or tumor suppressor proteins and Class II BMMs representing tumor marker proteins that provide information about cancer progression.

7. A method in accordance with claim 6 wherein said cancer therapy regimen is selected by evaluating said Class I BMMs for, upregulation or downregulation and evaluating said Class II BMMs if any of said Class I BMMs are upregulated or downregulated.

8. A method in accordance with claim 7 wherein said cancer therapy regimen is selected by evaluating said Class I BMMs to determine if only one Class I BMM is upregulated or downregulated, and if so, designating the patient as being possibly precancerous.

9. A method in accordance with claim 7 wherein said cancer therapy regimen is selected by evaluating said Class I BMMs to determine if only two Class I BMMs are upregulated or downregulated, and if so, designating the patient as being precancerous.

10. A method in accordance with claim 7 wherein said cancer therapy regimen is selected by evaluating said Class I BMMs to determine if three or more Class I BMMs are upregulated or downregulated, and if so, designating the patient as being cancerous.

11. A method for medical diagnosis and treatment of cancer, comprising:

obtaining an assay evaluation sample from a patient;

simultaneously testing said assay evaluation sample for upregulated or downregulated biomolecular markers (BMMs) representing a cancer protein pattern; and

selecting a cancer therapy regimen based on said cancer protein pattern.

12. A method in accordance with claim 11 wherein said assay evaluation sample comprises a homogenate of a solid tumor sample obtained from the patient.

13. A method in accordance with claim 11 wherein said assay evaluation sample comprises a blood serum/plasma sample obtained from the patient.

14. A method in accordance with claim 11 wherein said testing step is completed within 24-48 hours of obtaining said assay evaluation sample.

15. A method in accordance with claim 11 wherein said cancer therapy regimen is a first line cancer therapy regimen.

16. A method in accordance with claim 11 wherein said cancer therapy regimen is a first line radiotherapy regimen.

17. A method in accordance with claim 11 wherein said cancer therapy regimen is a chemotherapy regimen using a suite of chemotherapy agents directly corresponding to said cancer protein pattern.

18. A method in accordance with claim 17 wherein said chemotherapy agents are protein modulating drugs that each respectively modulate one BMM of said cancer protein pattern.

19. A method in accordance with claim 11 wherein said testing step includes simultaneously testing said assay evaluation sample for Class I BMMs representing either tumor promoting or tumor suppressor proteins and Class II BMMs representing tumor marker proteins that provide information about cancer progression.

20. A method for characterizing a cancer tumor for medical diagnosis and treatment, comprising:

obtaining an assay evaluation sample from a patient, said assay evaluation sample being either a homogenate of a solid tumor sample obtained from the patient or a blood serum/plasma sample obtained from the patient;

determining a cancer protein pattern based on detected nonbasal levels of biomolecular markers (BMMs) associated with the patient'"'"'s tumor;

selecting a cancer therapy regimen based on said cancer protein pattern for eradicating the tumor;

said cancer therapy regimen being a first line therapy regimen customized to target cells that express BMMs in said cancer protein pattern above or below basal levels;

said BMMs including proteins that can be modulated by protein modulating drugs and said cancer therapy regimen including protein modulating drugs corresponding to one or more of said BMMs;

said protein modulating drugs being selectively combined into a chemo-suite that directly corresponds to said BMM pattern;

said BMMs including Class I BMMs representing either tumor promoting or tumor suppressor proteins and Class II BMMs representing tumor marker proteins that provide information about cancer progression;

said cancer therapy regimen being selected by evaluating said Class I BMMs for upregulation or downregulation and evaluating said Class II BMMs if any of said Class I BMMs are upregulated or downregulated;

said cancer therapy regimen being selected by evaluating said Class I BMMs to determine if only one Class I BMM is upregulated or downregulated, and if so, designating the patient as being possibly precancerous;

said cancer therapy regimen being further selected by evaluating said Class I BMMs to determine if only two Class I BMMs are upregulated or downregulated, and if so, designating the patient as being precancerous; and

said cancer therapy regimen being further selected by evaluating said Class I BMMs to determine if three or more Class I BMMs are upregulated or downregulated, and if so, designating the patient as being cancerous.

21. A method for characterizing a cancer tumor for medical diagnosis and treatment, comprising:

determining a cancer protein pattern based on detected nonbasal levels of biomolecular markers (BMMs) associated with a patient'"'"'s tumor;

selecting a cancer therapy regimen based on said cancer protein pattern for eradicating the tumor; and

said method being specific to one or more particular cancer types and implemented as either a basic profile comprising a first set of BMMs or a comprehensive profile comprising said first set of BMMs and a second set of BMMs.

22. A method in accordance with claim 21 wherein said method is implemented as a basic ovarian profile with said first set of BMMs comprising ER/PR, Her2/neu, MRP, LRP and EGFR.

23. A method in accordance with claim 21 wherein said method is implemented as a comprehensive ovarian profile with said first and second sets of BMMs comprising ER/PR/AR, Her2/neu, MRP, LRP, EGFR, CA-125, CU-18, PCNA, DF 3, uPA.

24. A method in accordance with claim 21 wherein said method is implemented as a basic ovarian/peritoneal profile with said first set of BMMs comprising S-100, PCNA, MDR-1, EGFR, ER/PR/AR.

25. A method in accordance with claim 21 wherein said method is implemented as a comprehensive ovarian/peritoneal profile with said first and second sets of BMMs comprising S-100, PCNA, MDR-1, EGFR, ER/PR/AR, Ki-67, p53, Her2/neu, MRP, LRP, EGFR, CA-125, uPA.

26. A method in accordance with claim 21 wherein said method is implemented as a basic ovarian/gall bladder/peritoneal profile with said first set of BMMs comprising S-100, PCNA, MDR-1, EGFR ER/PR/AR, PP, p53, c-myc.

27. A method in accordance with claim 21 wherein said method is implemented as a comprehensive ovarian/gall bladder/peritoneal profile with said first and second sets of BMMs comprising S-100, PCNA, MDR-1, EGFR ER/PR/AR, PP, MRP, S-100, NSE, LMW Keratin, p53, TS, CD43, CEA, CD31, CA 242, c-myc, PDECGF, VIP.

28. A method in accordance with claim 21 wherein said method is implemented as a basic ademo-carcinoma profile with said first set of BMMs comprising ACTH, B72.3, BCA225, Bcl-2, CA15.3.

29. A method in accordance with claim 21 wherein said method is implemented as a comprehensive ademo-carcinoma profile with said first and second sets of BMMs comprising ACTH, B72.3, BCA225, Bcl-2, CA15.3, CA125, CEA/D-14, CyclinD1, PCNA, Ki-67, MRP, MDR-1.

30. A method in accordance with claim 21 wherein said method is implemented as a basic bladder profile with said first set of BMMs comprising p53, Her2/neu (p185), PCNA, MDR-1, EGFR.

31. A method in accordance with claim 21 wherein said method is implemented as a comprehensive bladder profile with said first and second sets of BMMs comprising p53, Her2/neu (p185), PCNA, MDR-1, EGFR, Ki-67, pan-ras, Bcl-2, Bcl-x, Rb.

32. A method in accordance with claim 21 wherein said method is implemented as a basic brain profile with said first set of BMMs comprising p53, Her2/neu, MGMT, Ki-67, MDR-1, GFAP, Syn.

33. A method in accordance with claim 21 wherein said method is implemented as a comprehensive brain profile with said first and second sets of BMMs comprising p53, Her2/neu, MGMT, Ki-67, MDR-1, GFAP, Syn, CD35, CD31, PCNA, VEGFR, PDGFR.

34. A method in accordance with claim 21 wherein said method is implemented as a basic breast profile with said first set of BMMs comprising ER/PR, Her2/neu, TS, BCA-125, MDR-1, MRP.

35. A method in accordance with claim 21 wherein said method is implemented as a comprehensive breast profile with said first and second sets of BMMs comprising ER/PR, Her2/neu, TS, BCA-125, MDR-1, MRP, CA-125, p53, CD31, CA 125, DF 3, VEGFR.

36. A method in accordance with claim 21 wherein said method is implemented as a basic colon/bowel profile with said first set of BMMs comprising p53, TS, CD43, CEA, PCNA.

37. A method in accordance with claim 21 wherein said method is implemented as a comprehensive colon/bowel profile with said first and second sets of BMMs comprising p53, TS, CD43, CEA, PCNA, MDR-1, CD31, CA 242, c-myc, PDECGF, VIP.

38. A method in accordance with claim 21 wherein said method is implemented as a basic endometrial profile with said first set of BMMs comprising ER/PR, Ki-67, p53, MDR-1.

39. A method in accordance with claim 21 wherein said method is implemented as a comprehensive endometrial profile with said first and second sets of BMMs comprising ER/PR, Ki-67, p53, MDR-1, CD31, CA-125, MPR, TSP, ras.

40. A method in accordance with claim 21 wherein said method is implemented as a basic lung profile with said first set of BMMs comprising p53, LRP, NSE, MDR-1 CEA, CA-125.

41. A method in accordance with claim 21 wherein said method is implemented as a comprehensive lung profile with said first and second sets of BMMs comprising p53, LRP, NSE, MDR-1 CEA, CA-125, bcl-2, Cyfra 21-1, CA 19-9, MGMT, MRP.

42. A method in accordance with claim 21 wherein said method is implemented as a basic melanoma profile with said first set of BMMs comprising MDR-1, p53, CD31, HMB-45, MRP, EGFR, Involucrin.

43. A method in accordance with claim 21 wherein said method is implemented as a comprehensive melanoma profile with said first and second sets of BMMs comprising MDR-1, p53, CD31, HMB-45, MRP, EGFR, Involucrin, Bcl-2, c-myc, PCNA, Ki67, NIKI.

44. A method in accordance with claim 21 wherein said method is implemented as a basic oral profile with said first set of BMMs comprising p53, MDR-1, MRP, EGFR, PCNA, CA-125.

45. A method in accordance with claim 21 wherein said method is implemented as a comprehensive oral profile with said first and second sets of BMMs comprising p53, MDR-1, MRP, EGFR, PCNA, CA-125.

46. A method in accordance with claim 21 wherein said method is implemented as a basic peritoneal profile with said first set of BMMs comprising CA19.9, Gastrin, S-100, PCNA, NSE.

47. A method in accordance with claim 21 wherein said method is implemented as a comprehensive peritoneal profile with said first and second sets of BMMs comprising CA19.9, Gastrin, S-100, PCNA, NSE, MDR, MRP, Ki-67, p53, EGFR.

48. A method in accordance with claim 21 wherein said method is implemented as a basic prostrate profile with said first'"'"'set of BMMs comprising AR, HPAP, PSMA, c-erb-2, Ki-67, GRP.

49. A method in accordance with claim 21 wherein said method is implemented as a comprehensive prostrate profile with said first and second sets of BMMs comprising AR, HPAP, PSMA, c-erb-2, Ki-67, GRP, p53, MDR-1, P-cadherin, VEGF, CD31.

50. A method in accordance with claim 21 wherein said method is implemented as a basic sarcoma profile with said first set of BMMs comprising p53, MDR-1, MRP, EGFR, O13.

51. A method in accordance with claim 21 wherein said method is implemented as a comprehensive sarcoma profile with said first and second sets of BMMs comprising p53, MDR-1, MRP, EGFR, O13, VEGR, Bcl-2, c-myc, PCNA, Ki-67.

52. A method in accordance with claim 21 wherein said method is implemented as a basic stomach profile with said first set of BMMs comprising CA19.9, Gastrin, PP, PCNA, MDR-1, S-100, HBP-P.

53. A method in accordance with claim 21 wherein said method is implemented as a comprehensive stomach profile with said first and second sets of BMMs comprising CA19.9, Gastrin, PP, PCNA, MDR-1, S-100, HBP-P, NSE, LMW Keratin, Villin.

54. A method in accordance with claim 21 wherein said method is implemented as a basic thyroid profile with said first set of BMMs comprising Iodine-R, Thyro-R, TSH-R, PCNA, p53.

55. A method in accordance with claim 21 wherein said method is implemented as a comprehensive thyroid profile with said first and second sets of BMMs comprising Iodine-R, Thyro-R, TSH-R, PCNA, p53, PTH-R, MDR-1, MRP.

56. A method in accordance with claim 21 wherein said method is implemented as a basic unknown primary site profile with said first set of BMMs comprising p53, Her2/neu, MDR-1, PCNA, CD31, CA-125.

57. A method in accordance with claim 21 wherein said method is implemented as a comprehensive unknown primary site profile with said first and second sets of BMMs comprising p53, Her2/neu, MDR-1, PCNA, CD31, CA-125, CD34, Ki-67, MPR, LRP, CEA.

58. A method for characterizing a cancer tumor for medical diagnosis and treatment, comprising:

determining a cancer protein pattern based on detected nonbasal levels of biomolecular markers (BMMs) associated with a patient'"'"'s tumor;

selecting a cancer therapy regimen based on said cancer protein pattern for eradicating the tumor; and

said method being implemented as a panel comprising a set of BMMs selected to provide cancer diagnostic information.

59. A method in accordance with claim 58 wherein said method is implemented as an angiogenesis panel with said BMMs comprising CD31, CD34, VEGFR, TSP-1, PDGFR-α

chain.

60. A method in accordance with claim 58 wherein said method is implemented as an angiogenesis panel with said BMMs comprising p53, TSP-1, CD31.

61. A method in accordance with claim 58 wherein said method is implemented as an apoptosis panel with said BMMs comprising P53, mdm-2, annexin, bcl-2, bax.

62. A method in accordance with claim 58 wherein said method is implemented as an apoptosis panel with said BMMs comprising P53, mdm-2, annexin, bcl-2, bax.

63. A method in accordance with claim 58 wherein said method is implemented as a carcinoma of unknown site panel with said BMMs comprising PCNA, p53, Her-2, MDR, ER/PR/AR.

64. A method in accordance with claim 58 wherein said method is implemented as a carcinoma of unknown site with metastasis to spine or bones panel with said BMMs comprising Her-2, LRP, MDR, CEA, CA125, CD43, PSMA.

65. A method in accordance with claim 58 wherein said method is implemented as a carcinoma vs. Lymphoma panel with said BMMs comprising LCA, c-kit/myeloid marker=CD117,Ki-67.

66. A method in accordance with claim 58 wherein said, method is implemented as an epithelial panel with said BMMs comprising Ber-EP4, B72.3, EGFR, EMA.

67. A method in accordance with claim 58 wherein said method is implemented as a growth factor receptor panel with said BMMs comprising c-erb-2, EGFR, c-erb-1, VEGFR, PDGFR, TGFR-I&

II.

68. A method in accordance with claim 58 wherein said method is implemented as a heat shock protein panel with said BMMs comprising HSP-PC96, HSP 70, HSP 90.

69. A method in accordance with claim 58 wherein said method is implemented as a hormone receptor panel with said BMMs comprising ER/PR/AR.

70. A method in accordance with claim 58 wherein said method is implemented as an invasion metastasis panel with said BMMs comprising ICAM, uPa, Pai-2, Bcl-x, TM.

71. A method in accordance with claim 58 wherein said method is implemented as a keratin panel with said BMMs comprising Keratins #39, 43, 50.

72. A method in accordance with claim 58 wherein said method is implemented as a keratin panel with said BMMs comprising Keratins #45, 56.

73. A method in accordance with claim 58 wherein said method is implemented as a keratin panel with said BMMs comprising Keratins #34, 39, 40, 43, 48, 50, 50.6.

74. A method in accordance with claim 58 wherein said method is implemented as a keratin panel with said BMMs comprising Keratins #40-68.

75. A method in accordance with claim 58 wherein said method is implemented as a lymph node and bone marrow micrometastasis panel with said BMMs comprising LK/AE-1, CD31, CD34.

76. A method in accordance with claim 58 wherein said method is implemented as a lymphoma versus carcinoma panel with said BMMs comprising LCA, c-kit/myeloid marker=CD117, Ki-67.

77. A method in accordance with claim 58 wherein said method is implemented as a multidrug resistance panel with said BMMs comprising MDR-1, MPR, MGMT.

78. A method in accordance with claim 58 wherein said method is implemented as a multidrug resistance panel with said BMMs comprising TS, LRP, Topoisomerase I&

II.

79. A method in accordance with claim 58 wherein said method is implemented as a neural panel with said BMMs comprising CD56, GFAP, Leu7, MBP, NF, NSE, β

2-Microglobulin, Syn, NSE, Ubiguitin.

80. A method in accordance with claim 58 wherein said method is implemented as a neuroendocrine panel with said BMMs comprising PGP 9.5, NSE, Chromogranin A, CEA.

81. A method in accordance with claim 58 wherein said method is implemented as a neuroendocrine gastrin panel with said BMMs comprising Bombesin, CA19.9, CD56, Leu7.

82. A method in accordance with claim 58 wherein said method is implemented as an occult metastasis panel with said BMMs comprising ICAM, uPA, Pai-2, Bcl-x, TM.

83. A method in accordance with claim 58 wherein said method is implemented as an occult metastasis panel with said BMMs comprising p53, TSP-1, CD31.

84. A method in accordance with claim 58 wherein said method is implemented as an oncogene/tumor suppressor gene panel with said BMMs comprising TNFR, TGFR, c-myc, p53, ras.

85. A method in accordance with claim 58 wherein said method is implemented as an oncogenene/tumor suppressor gene panel with said BMMs comprising c-fos, c-jun, c-myc, ras.

86. A method in accordance with claim 58 wherein said method is implemented as a pituitary panel with said BMMs comprising GH, IGF-I, TSH, Adrenocorticotropin, Prolactin.

87. A method in accordance with claim 58 wherein said method is implemented as a proliferative panel with said BMMs comprising Ki-67, c-erb-2, PCNA.

88. A method in accordance with claim 58 wherein said method is implemented as an T &

B lymphocytes panel with said BMMs comprising CD3, CD19/Leu12, CD45RO/A6, Leu17 (T-cells, B-cells, [Helper, Inducer T-cells], Activated T&

B cells).

89. A method in accordance with claim 58 wherein said method is implemented as an unconventional multidrug resistance panel with said BMMs comprising p53, bcl-2.

90. A method in accordance with claim 58 wherein said method is implemented as an undifferentiated carcinoma panel with said BMMs comprising p53, Rb, APC, MCC, simple epithelial cytokeratins and squamous epithelial cytokeratins.

91. A method in accordance with claim 58 wherein said method is implemented as an undifferentiated tumor panel with said BMMs comprising calretinin, mucicarmine, CEA, B72.3.

92. A method in accordance with claim 58 wherein said method is implemented as a white blood cell count panel with said BMMs comprising MCG, CD3, CD19/Leu-12, CD41/GPIIB/lIIA, CD45 (Macrophages, T-cells, B-cells, [platelets, megakaryocytes, megakaryoblasts], leukocytes).

93. A method in accordance with claim 58 wherein said method is implemented as a white blood cell count panel with said BMMs comprising MCG, CD3/Leu3a&

b, CD45, CD14/MO2 (Magrophages, Helper T-cells, [Mature monocytes;

granulocytes], Leukocytes).

94. A method in accordance with claim 58 wherein said method is implemented as a white blood cell count panel with said BMMs comprising T&

B cells=CD3, CD19/Leu12, CD45RO/A6, Leu17 (T-cells, B-cells, (Helper, Inducer T-cells], Activated T&

B cells).