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Methods for assessing and treating cancer

An oncogene, farnesyltransferase technology, used in the evaluation and treatment of cancer

Inactive Publication Date: 2006-01-18
VERIDEX LCC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, Ras is not the only protein of this type associated with cancer

Method used

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  • Methods for assessing and treating cancer
  • Methods for assessing and treating cancer
  • Methods for assessing and treating cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0116] Example 1: Microarray Analysis

[0117] From Zarnestra diluted with PBS and centrifuged with Ficoll-3,5-bis(acetylamino)-2,4,6-triiodobenzoic acid (1.077g / ml) TM FTI (active ingredient, (R)-6-[amino(4-chlorophenyl)(1-methyl- 1H -Imidazol-5-yl)methyl]-4-(3-chlorophenyl)1-methyl- 2(1H) -quinolinone)-treated patients, bone marrow samples were collected before and after treatment. Leukocytes were washed twice with PBS, resuspended in FBS containing 10% DMSO, and immediately frozen at -80°C. The samples were thawed at 37°C and 10 x volume of RPMI with 20% FBS was added dropwise over a period of 5 minutes. Cells were centrifuged at 500 g for 10 minutes and resuspended in 10 ml PBS containing 2 mM EDTA and 0.5% BSA. Samples were then passed through a 70 [mu]M filter (Becton Dickinson Labware, Franklin lakes, NJ) to remove any cell clumps. Cell viability was determined by trypan blue dye exclusion assay. The mean viability of bone marrow samples at thaw was 35% (range ...

Embodiment 2

[0125] Example 2: Leukemia cell antigen expression

[0126] Leukemic blast cells are known to express the surface antigens CD33 and CD34. 95% and 55% of patients' myeloid leukemia cells were positive for CD33 and CD34, respectively. The average percentage of antigen-expressing cells in each sample was 13% for CD34 and 43% for CD33. Chi-squared analysis was performed to investigate the correlation between antigen expression levels and patient outcomes. Cutoffs of 15% and 60% were chosen for CD34 and CD33 levels, respectively. Low expression of CD33 and CD34 (less than about 15% of the CD34 cell population positive and less than about 60% of the CD33 cell population positive) was associated with patient response to Zarnestra TM Correlation (p=0.137, p=0.052, respectively). High expression of both antigens (greater than about 15% positive for the CD34 cell population and less than about 60% positive for the CD33 cell population) was also positively correlated with high blast ...

Embodiment 3

[0127] Example 3: Leukemia blast count analysis

[0128] Analysis of CD33 and CD34 antigen expression suggested that leukemic blasts were associated with patient response. Means of sites and DCL blast count measurements were calculated and a Student's t-test was performed to investigate whether blast counts were associated with patient response in AML patients. Of a total of 199 patients evaluated, 24 had CR, CRp, PR, or SD, and the percentage of blasts correlated significantly with patient output (p=0.0006). Responders had lower numbers of blast cells (average 34%) than patients with progressive disease (average 51%). Only one of a total of 24 responders (defined as having SD) had a blast count above 60%. Chi-square analysis of all evaluable patients also found a significant correlation between high blast count and treatment resistance (X 2 =9.53).

[0129] Kaplan-Meier analysis found that patients with low blast counts ( figure 2 ). These analyzes indicated that patient...

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Abstract

Methods for treating cancer, and preferably hematological malignancy, patients include analyzing gene expression profiles and / or molecular markers of a patient to determine whether the patient is likely to respond to treatment with farnesyl transferase inhibitors (FTIs) and, optionally, other therapeutics. The methods are also useful for monitoring patient therapy and for selecting a course of therapy. Genes modulated in response to FTI treatment are provided and are used in formulating the profiles.

Description

[0001] Cross-references to related applications [0002] This application is a continuation-in-part of US Patent Application Serial No. 10 / 611,446, filed July 1, 2003, and claims the benefit of priority therefrom. [0003] Statement Regarding Federally Funded Research or Development [0004] Not applicable. [0005] Reference to the "Sequence Listing" [0006] The attached "Sequence Listing" and the computer program delivered on compact disc are hereby incorporated by reference. Background of the invention [0007] The present invention relates to the diagnosis, prognosis and treatment of cancer based on the detection of molecular markers and / or gene expression analysis. [0008] Some cancer-related molecules, such as Ras, must be farnesylated by farnesyltransferases to interact with the inner leaflet of the plasma membrane and involve multiple signaling pathways. However, Ras is not the only protein of this kind that has been associated with cancer. Farnesyltransferase i...

Claims

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Application Information

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IPC IPC(8): C12Q1/68A61K31/4709A61P35/00C07K16/32G01N33/50
CPCA61K31/47C07K16/32G01N33/5011C12Q2600/158C12Q1/6886C12Q2600/106G01N2800/52A61P35/00A61P43/00C07K16/18
Inventor M·拉波尼
Owner VERIDEX LCC
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