US2019360057A1PendingUtilityA1

Diagnostic and therapeutic methods and compositions involving pten and breast cancer

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Assignee: UNIV TEXASPriority: Nov 5, 2003Filed: Jun 18, 2019Published: Nov 28, 2019
Est. expiryNov 5, 2023(expired)· nominal 20-yr term from priority
Inventors:Dihua YuXiaoyan ZhouYoichi NagataFrancisco J. EstevaAysegul A. Sahin
A61P 35/00G01N 33/57515C12Q 1/6886G01N 33/573C12Q 1/42C12Q 2600/106G01N 33/5011Y10T436/25G01N 33/57415
61
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Claims

Abstract

Patients with ErbB2-overexpressing cancers can be given an ErbB2 targeting agent as a therapeutic regimen but not all patients are responsive. The present invention concerns the diagnostic, prognostic and therapeutic methods and compositions for evaluating potential efficacy of an ErbB2 targeting agent in ErbB2-overexpressing cancers by evaluating PTEN expression, which is predictive of responsiveness or resistance to ErbB2 targeting agents such as trastuzumab. Low PTEN expression is predictive of a patient who will respond poorly to trastuzumab.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . A method for administering a treatment regimen comprising an effective amount of a PI3K inhibitor, said method comprising:
 (1) assaying a patient sample comprising at least one test cancer cell to evaluate PTEN expression in said at least one test cancer cell;   (2) comparing the PTEN expression in (1) to a reference PTEN expression in reference cancer cells of a reference cohort of patients who are not candidates for said treatment regimen; and   (3) administering said treatment regimen to a test patient for whom said at least one test cancer cell is evaluated in (1) to have PTEN expression that is lower than the reference PTEN expression in (2).   
     
     
         2 . The method of  claim 1 , wherein said PTEN expression in (1) is no more than 50% said PTEN expression in (2). 
     
     
         3 . The method of  claim 1 , wherein the at least one test cancer cell is selected from the group consisting of breast cancer, lung cancer, ovarian cancer, brain cancer, gastrointestinal tract cancer, salivary duct cancer, endometrial cancer, prostate cancer, head & neck cancer, glioma, pancreatic cancer, hepatocellular cancer, myeloma, soft tissue sarcoma, and non-small cell lung cancer. 
     
     
         4 . The method of  claim 1 , wherein the at least one test cancer cell is breast cancer. 
     
     
         5 . The method of  claim 1 , wherein PTEN expression is evaluated by sequencing PTEN nucleic acid of said patient sample. 
     
     
         6 . The method of  claim 5 , wherein PTEN nucleic acid is PTEN transcript. 
     
     
         7 . The method of  claim 5 , wherein PTEN nucleic acid is PTEN genomic DNA. 
     
     
         8 . The method of  claim 5 , wherein PTEN nucleic acid is PTEN cDNA. 
     
     
         9 . The method of  claim 8 , wherein the PTEN cDNA has the sequence of SEQ. ID NO. 1. 
     
     
         10 . The method of  claim 1 , wherein the patient sample comprises a biological sample selected from the group consisting of tissue biopsy or section, blood sample, lavage, swab, scrape, or nipple aspirate. 
     
     
         11 . The method of  claim 1 , wherein the patient sample comprises a tissue biopsy. 
     
     
         12 . The method of  claim 1 , wherein PTEN expression is evaluated by measuring PTEN transcription. 
     
     
         13 . The method of  claim 12 , wherein PTEN transcription is measured using at least one technique chosen from the group consisting of fluorescence in situ hybridization (FISH), RNA in situ hybridization (RISH), quantitative polymerase chain reaction, Northern blotting, or nuclease protection assays. 
     
     
         14 . The method of  claim 1 , wherein PTEN expression is evaluated by measuring PTEN gene copy number. 
     
     
         15 . The method of  claim 1 , wherein PTEN expression is evaluated by assaying PTEN gene methylation. 
     
     
         16 . The method of  claim 1 , wherein said test patient is not a candidate for treatment with trastuzumab because said patient is predicted to have a high probability of resistance for trastuzumab. 
     
     
         17 . The method of  claim 17 , wherein said test patient is predicted to have a high probability of resistance to trastuzumab based at least in part on PTEN expression in cancer cells of a test patient that is significant less than PTEN expression in a normal cell. 
     
     
         18 . The method of  claim 17 , wherein said normal cell is a non-cancerous cell. 
     
     
         19 . A method for administering a first treatment regimen comprising an effective amount of a PI3K inhibitor, said method comprising:
 (1) assaying a patient sample comprising at least one test cancer cell to evaluate PTEN expression in said at least one test cancer cell;   (2) comparing the PTEN expression in (1) to a reference PTEN expression in reference cancer cells of a reference cohort of patients who are not candidates for said treatment regimen; and   (3)(a) administering said treatment regimen to a test patient for whom said at least one test cancer cell is evaluated in (1) to have PTEN expression that is no more than 50% than the reference PTEN expression in (2); or   (3)(b) administering a second treatment regimen comprising trastuzumab to a test patient for whom said at least one test cancer cell is evaluated in (1) to have PTEN expression that is greater than 50% than the reference PTEN expression in (2).   
     
     
         20 . The method of  claim 19 , wherein the at least one test cancer cell is selected from the group consisting of breast cancer, lung cancer, ovarian cancer, brain cancer, gastrointestinal tract cancer, salivary duct cancer, endometrial cancer, prostate cancer, head & neck cancer, glioma, pancreatic cancer, hepatocellular cancer, myeloma, soft tissue sarcoma, and non-small cell lung cancer. 
     
     
         21 . The method of  claim 19 , wherein the at least one test cancer cell is breast cancer. 
     
     
         22 . The method of  claim 19 , wherein PTEN expression is evaluated by sequencing PTEN nucleic acid of said patient sample. 
     
     
         23 . The method of  claim 22 , wherein PTEN nucleic acid is PTEN transcript. 
     
     
         24 . The method of  claim 22 , wherein PTEN nucleic acid is PTEN genomic DNA. 
     
     
         25 . The method of  claim 22 , wherein PTEN nucleic acid is PTEN cDNA. 
     
     
         26 . The method of  claim 25 , wherein the PTEN cDNA has the sequence of SEQ. ID NO. 1. 
     
     
         27 . The method of  claim 19 , wherein the patient sample comprises a biological sample selected from the group consisting of tissue biopsy or section, blood sample, lavage, swab, scrape, or nipple aspirate. 
     
     
         28 . The method of  claim 19 , wherein the patient sample comprises a tissue biopsy. 
     
     
         29 . The method of  claim 19 , wherein PTEN expression is evaluated by measuring PTEN transcription. 
     
     
         30 . The method of  claim 29 , wherein PTEN transcription is measured using at least one technique chosen from the group consisting of fluorescence in situ hybridization (FISH), RNA in situ hybridization (RISH), quantitative polymerase chain reaction, Northern blotting, or nuclease protection assays. 
     
     
         31 . The method of  claim 19 , wherein PTEN expression is evaluated by measuring PTEN gene copy number. 
     
     
         32 . The method of  claim 19 , wherein PTEN expression is evaluated by assaying PTEN gene methylation.

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