Identification of Non-Small Cell Lung Carcinoma (NSCLC) Tumors Expressing PDGFR-alpha

Patent metadata

Field	Value
Publication number	US-2016193208-A1
Application number	US-201514847545-A
Country	US
Kind code	A1
Filing date	Sep 8, 2015
Priority date	Jul 1, 2005
Publication date	Jul 7, 2016
Grant date	—

Abstract

The invention discloses a previously unidentified subset of mammalian non-small cell lung carcinomas (NSCLC) in which platelet-derived growth factor receptor alpha (PDGFRα) is expressed and is driving the disease, and provides methods for identifying a mammalian NSCLC tumor that belongs to a subset of NSCLC tumors in which PDGFRα is expressed, and for identifying a NSCLC tumor that is likely to respond to a PDGFRα-inhibiting therapeutic. The invention also provides methods for inhibiting the progression of a mammalian NSCLC tumor in which PDGFRα is expressed, and for determining whether a compound inhibits the progression of a PDGFRα-expressing mammalian NSCLC tumor.

First claim

What is claimed is:

1 . A method for identifying a mammalian non-small cell lung carcinoma (NSCLC) tumor that belongs to a subset of NSCLC tumors in which platelet-derived growth factor receptor alpha (PDGFRα) is expressed, said method comprising the step of determining whether PDGFRα is expressed in a biological sample comprising cells from a NSCLC tumor using at least one PDGFRα specific reagent, wherein expression of PDGFRα in said biological sample identifies said NSCLC tumor as belonging to a subset of NSCLC tumors in which PDGFRα is expressed.

2 . The method of claim 1 , wherein said mammal is a human.

3 . The method of claim 1 , wherein identifying said NSCLC tumor as belonging to a subset of NSCLC tumors in which PDGFRα is expressed Identifies said NSCLC tumor as being likely to respond to a composition comprising at least one PDGFRα-inhibiting therapeutic.

4 . The method of claim 3 , wherein said PDGFRα-inhibiting therapeutic comprises a small molecule inhibitor of PDGFRα.

5 . The method of claim 4 , wherein said small molecule inhibitor of PDGFRα is Imatinib mesylate (STI-571).

6 . The method of claim 4 wherein said small molecule inhibitor of PDGFRα is an Imatinib mesylate (STI-571) analogue.

7 . The method of claim 6 , wherein said Imatinib mesylate (STI-571) analogue is selected from the group consisting of BAY 43-93006, XL-999 and SU11248.

8 . The method of claim 1 , wherein said biological sample comprises cells obtained from a tumor biopsy, a tumor fine needle aspirate, or a pleural effusion.

9 . The method of claim 1 , wherein said PDGFRα-specific reagent comprises a PDGFRα-specific antibody.

10 . The method of claim 9 , wherein said PDGFRα-specific antibody is a phosphorylation site-specific antibody.

11 . The method of claim 1 , wherein said PDGFRα-specific reagent comprises a heavy-isotope labeled peptide (AQUA peptide) that corresponds to a PDGFRα peptide sequence.

12 . The method of claim 11 , wherein said AQUA peptide is a peptide having a sequence selected from the group consisting of SEQ ID NOs: 3-8.

13 . The method of claim 1 , wherein said method is implemented in a flow-cytometry (FC), immuno-histochemistry (IHC), or immuno-fluorescence (IF) assay format.

14 . A method for determining whether a compound inhibits the progression of a mammalian NSCLC tumor belonging to a subset of NSCLC tumors in which PDGFRα is expressed, said method comprising the step of determining whether said compound inhibits the expression and/or activity of PDGFRα in said NSCLC tumor.

15 . The method of claim 14 , wherein inhibition of expression and/or activity of PDGFRα is determined by examining a biological sample comprising cells from said NSCLC tumor.

16 . The method of claim 14 , wherein inhibition of expression and/or activity of PDGFRα is determined using at least one PDGFRα-specific reagent.

17 . The method of claim 16 , wherein said PDGFRα-specific reagent comprises a phosphorylation-site specific antibody.

18 . A method for inhibiting the progression of a mammalian NSCLC tumor belonging to a subset of NSCLC tumors in which PDGFRα is expressed, said method comprising the step of inhibiting the expression and/or activity of PDGFRα in said tumor.

19 . The method of claim 18 , wherein expression and/or activity of PDGFRα is inhibited with composition comprising Imatinib mesylate (STI-571) and/or an analogue of Imatinib mesylate (STI-571).

20 . The method of claim 19 , wherein said analogue is selected from the group consisting of BAY 43-93006, XL-999 and SU11248.

Assignees

• Cell Signaling Technology Inc

Inventors

• Rikova Klarisa
• Polakiewicz Roberto
• Guo Ailan
• Crosby Katherine Eleanor
• Zeng Quingfu
• Lee Kimberly A

Classifications

• A61K31/506 Primary

  not condensed and containing further heterocyclic rings · CPC title

• G01N33/6893

  related to diseases not provided for elsewhere · CPC title

• G01N2333/71

  for growth factors; for growth regulators · CPC title

• G01N33/5752

  of the lungs · CPC title

• G01N33/57423

  Physics · mapped topic