Anaplastic Lymphoma Kinase In Kidney Cancer

a technology of anaplastic lymphoma and kidney cancer, which is applied in the field of anaplastic lymphoma kinase in kidney cancer, can solve the problems of uncontrollable cell growth and proliferation, and affecting the normal function of cells

Inactive Publication Date: 2012-04-26
CELL SIGNALING TECHNOLOGY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0027]In various embodiments of all of the aspects of the invention, a patient from whom said biological sample is obtained is diagnosed as having a mammalian kidney cancer or suspected mammalian kidney cancer driven by the polypeptide with ALK kinase activity. In some embodiments, the patient is administered pharmaceutical composition comprising an ALK-inhibiting therapeutic (e.g., PF-02341066, NVT TAE-684, AP26113, CEP-14083, CEP-14513, CEP11988, WHI-P131 or WHI-P154).
[0028]In various embodiments of all of the aspects of the invention, the expression and/or activity of the polypeptide with ALK kinase activity is inhibited with a composition comprising an ALK-inhibiting therapeutic. In some embodiments, the ALK-inhibiting therapeutic is PF-02341066 (also known as crizotinib). In some embodiments, the ALK-inhibiting therapeutic is NVT TAE-684, AP26113, or CEP-14083, CEP-14513, CEP11988, WHI-P131 and WHI-P154.
[0029]In still another aspect, the invention provides methods for diagnosing kidney cancer in a patient (also referred to as a subje

Problems solved by technology

Many cancers are characterized by disruptions in cellular signaling pathways that lead to aberrant control of cellular processes, or to uncontrolled growth and proliferation of cells.
The development of such drugs represents a significant advance over the conventional therapies for CML and ALL, chemotherapy and radiation, which are plagued by well known side-effects and are often of limited effect since they fail to specifically target the underlying causes of the malignancies.

Method used

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  • Anaplastic Lymphoma Kinase In Kidney Cancer
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  • Anaplastic Lymphoma Kinase In Kidney Cancer

Examples

Experimental program
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example 1

Identification of ALK or ALK Fusion Polypeptides in Kidney Cancer Patients

[0209]Tissue microarrays comprised of samples of cancers of the breast, pancreas, prostate, bladder, endometrium, kidney and various metastases were obtained from BioChain Institute, Inc., Hayward, Calif.

[0210]Tissue arrays were deparaffinized through three changes of xylene for 5 minutes each, then rehydrated through two changes of 100% ethanol and 2 changes of 95% ethanol, each for 5 minutes. Slides were rinsed for 5 minutes each in three changes of diH2O, then were subjected to antigen retrieval in a Decloaking Chamber (Biocare Medical, Concord, Calif.) as follows. Slides were immersed in 250 ml 1.0 mM EDTA, pH 8.0 in a 24 slide holder from Tissue Tek. The Decloaking Chamber was filled with 500 ml diH2O, the slide holder was placed in the chamber touching the heat shield, and retrieval was performed with the following settings as set by the manufacturer: SP1 125° C. for 30 seconds and SP2 90° C. for 10 seco...

example 2

Evaluation of ALK in Kidney Using FISH Analysis

[0215]ALK was analyzed by fluorescent in situ hybridization (FISH) in a lymphoma tissue of the kidney (Z7020052 I6 / J6) and a squamous cell carcinoma tissue of the kidney (Z6020052 G8 / H8) with the use of a break-apart probe specific to the ALK locus (Vysis LSI ALK Dual Color, Break Apart Rearrangement Probe; Abbott Molecular). The Vysis probe contains two differently labeled probes on opposite sides of the breakpoint of the ALK gene: one approximately 250 kb probe for the telomeric side of the ALK breakpoint is labeled with SpectrumOrange and the centromeric probe is approximately 300 kb and labeled with SpectrumGreen. When hybridized with the LSI ALK Dual Color, Break Apart Rearrangement Probe, the 2p23 ALK region in its native state is seen as two immediately adjacent or fused orange / green (yellow) signals. Paraffin embedded tissue sections were re-hydrated and incubated for 1 hour in TE buffer pH 8 in boiling water. Sections were dige...

example 3

Evaluation of MDCK for ALK and c-Met in Western Blot Experiment

[0216]U.S. Patent Application Publication No. 2008 / 0300273, herein incorporated by reference, describes the application of the c-Met and ALK inhibitor, crizotinib (PF-02341066) to Madin-Darby Canine Kidney (MDCK) cell lines to reduce HGF-stimulated cell scattering.

[0217]HGF-stimulated MDCK cell lines were evaluated to assess whether crizotinib was acting by inhibition of c-Met or ALK using antibodies specific for either c-Met, ALK or ALK fusion polypeptides.

[0218]MDCK were maintained in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum. The cells were serum-starved overnight and then either stimulated with hepatocyte growth factor (HGF) (50 ng / ml) at 37° C. for 5 min or 24 h, or serum-starved for an additional 5 min or 24 h. Cells were then washed in ice-cold PBS, treated with 1× Cell Lysis Buffer (20 mM Tris-HCl (pH7.5), 150 mM NaCl, 1 mM Na2EDTA, 1 mM EGTA, 1% Triton, 2.5 mM sodium pyrophospha...

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Abstract

The invention provides methods to identify, diagnose, and treat kidney cancer through the detection of expression and / or activity of anaplastic lymphoma kinase (ALK). The detection of the presence of a polypeptide with ALK kinase activity (e.g., by detecting expression and / or activity of the polypeptide), identify those kidney cancers that are likely to respond to an ALK-inhibiting therapeutic.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application claims priority to U.S. provisional patent application Ser. No. 61 / 371,525 filed Aug. 6, 2010, the entire contents of which is hereby incorporated by reference.FIELD OF THE INVENTION[0002]The invention relates generally to proteins and genes involved in cancer (e.g., kidney cancer), and to the detection, diagnosis and treatment of cancer.BACKGROUND OF THE INVENTION[0003]Many cancers are characterized by disruptions in cellular signaling pathways that lead to aberrant control of cellular processes, or to uncontrolled growth and proliferation of cells. These disruptions are often caused by changes in the activity of particular signaling proteins, such as kinases.[0004]Aberrant expression of protein kinase proteins can be the causative agent of (and the driver of) cancer. Aberrant expression can be caused by the fusion of the protein (or kinase portion thereof) with a secondary protein (or portion there), expression of a tru...

Claims

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Application Information

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IPC IPC(8): A61K31/496A61K31/4545C12Q1/48C12Q1/68G01N33/573
CPCG01N33/57438G01N2800/52G01N2333/70596A61K31/4162A61K31/4545A61K31/517C12Q1/6886C12Q2600/112G01N33/57484
Inventor HAACK, HERBERTCROSBY, KATHERINE ELEANORRIMKUNAS, VICTORIA MCGUINNESSSILVER, MATTHEW REN
Owner CELL SIGNALING TECHNOLOGY
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