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Use of VEGFR-2 inhibitors for treating metastatic cancer

A technology of VEGFR-2 and inhibitor, which is applied in the field of VEFR-2 inhibitor for the treatment of metastatic cancer, can solve the problem that tumor spread to other tissues is not very effective.

Inactive Publication Date: 2010-11-10
BRISTOL MYERS SQUIBB CO
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Chemotherapy is therefore a non-specific modality of treatment that affects all proliferating cells, including normal cells, causing unwanted and often severe side effects such as immunosuppression, pancytopenia (suppression of bone marrow cell growth accompanied by anemia, Thrombocytopenia and leukopenia), diarrhea, nausea, or alopecia (hair loss)
[0011] In general, existing systemic therapies often have little effect on pre-existing micrometastases in distant organs (lung, liver, bone marrow, or brain), and they are not very effective at preventing tumor spread to other tissues

Method used

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  • Use of VEGFR-2 inhibitors for treating metastatic cancer

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Embodiment approach

[0316] In some embodiments, it may be preferable to glycosylate the proteins used in the invention. Preferably, such proteins are fibronectin based scaffolds such as Adnectins TM . But Adnectins TM Typically no glycosylation sites are included, which can be engineered into the protein.

[0317] Glycosylation of proteins is usually either N-linked or O-linked. N-linked means that the carbohydrate moiety is attached to the side chain of an asparagine residue. The tripeptide sequences asparagine-X-serine and asparagine-X-threonine, where X is any amino acid except proline, are the recognition sequences for enzymatic attachment of the carbohydrate moiety to the asparagine side chain . These tripeptide sequences can be engineered into proteins of the invention, particularly fibronectin-based scaffolds such as Adnectins TM , and their corresponding polynucleotides. Thus, the presence of either of these tripeptide sequences in a polypeptide can potentially create a glycosylati...

Embodiment 1

[0382] Comp-I was significantly more active than bevacizumab in an orthotopic model of tumor metastasis. On day 0, human MDA-MB-231 breast cancer cells were implanted into mouse mammary fat pads (1×10 6 MDA-MB-231 breast cancer cells). The resulting tumor was resected on day 24 and treatment was started 4 days later (average tumor volume at resection was 400mm 3 ). The treatment groups were as follows: Control: PBS, Comp-I: 30 mg / kg, Bevacizumab 5 mg / kg (100 μL IP injection, twice a week). At sacrifice, the extent of local regrowth and the number of lung metastases were assessed. Comp-I produced fewer macroscopic metastases per mouse than bevacizumab. Furthermore, Comp-I had a significant effect on the incidence of metastasis in the study. Only 30% of Comp-I treated mice showed lung metastases compared to 74% of bevacizumab treated animals and 84% of controls (see figure 1 ).

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Abstract

The present application provides compositions and methods for treating metastatic cancer. Patients having or at risk of developing metastases may be treated. Compositions useful for the invention include VEGFR-2 specific inhibitors.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit of US Provisional Application Serial No. 60 / 965,574, filed August 20, 2007, which is hereby incorporated by reference in its entirety. technical field [0003] The present invention relates to the treatment of metastatic cancer with novel proteins that block the VEGF-VEGFR pathway mediating biology and pathology. The invention also relates to pharmaceutical preparations of the new protein, derivatives of said protein, and their use in the treatment of metastatic cancer. Background technique [0004] The formation of malignant tumor metastases is initiated by distant primary tumors in vivo. Malignant tumor metastasis is one of the most serious hazards of cancer, and currently there is no satisfactory treatment for malignant tumor metastasis. Cancer tumor metastasis is the main cause of failure of most therapies in the treatment of the disease as patients succumb to multiple tumors. ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/17A61K31/00A61K39/395A61P35/04
CPCC07K2318/20A61K38/17C07K16/2863A61K2039/505C07K2316/96C07K2317/73A61P35/04A61P43/00A61K2300/00
Inventor 罗尼·马姆卢克
Owner BRISTOL MYERS SQUIBB CO
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