Treatment of lung cancer with a PARP inhibitor in combination with a growth factor inhibitor

A growth factor and inhibitor technology, used in the treatment of lung cancer and non-small cell lung cancer, can solve the problems of inappropriate treatment and difficult to treat cancer variants.

Inactive Publication Date: 2012-01-04
BIPAR SCI INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] While there are limited treatment options for cancer treatment, variants of cancer, including lung cancer, are particularly difficult to treat because they can

Method used

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  • Treatment of lung cancer with a PARP inhibitor in combination with a growth factor inhibitor
  • Treatment of lung cancer with a PARP inhibitor in combination with a growth factor inhibitor
  • Treatment of lung cancer with a PARP inhibitor in combination with a growth factor inhibitor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment approach

[0172] Some embodiments employ compounds of the formula:

[0173]

[0174] where R 1 , R 2 , R 3 , or R 4 each independently selected from the group consisting of hydrogen, hydroxyl, amino, (C 1 -C 6 ) alkyl, (C 1 -C 6 ) alkoxy, (C 3 -C 7 ) cycloalkyl, halo and phenyl, wherein the R 1 , R 2 , R 3 , or R 4 At least three of the four substituents are always hydrogen.

[0175] One embodiment relates to the following formula II benzopyrone compound

[0176]

[0177] In yet another embodiment, the compound used in the methods described herein is

[0178]

[0179] Further details regarding benzopyrone compounds are found in US Patent 5,484,951, which is hereby incorporated by reference in its entirety.

[0180] It is possible that the most potent and effective PARP inhibitors (i.e. possible candidates for drug development) are not yet available in the scientific literature but are undergoing clinical trials or could end up in published patents and pending pat...

Embodiment 1

[0330] Example 1: Combination of BA with EGFR inhibitors

[0331] cell culture

[0332] Lung adenocarcinoma HCC827 cells were cultured in Duibecco's modified Eagle's medium containing 10% fetal bovine serum. HCC827 cells harbor the E746_A750del mutation of EGFR and were used to examine the effect of gefitinib (IRESSA) in combination with the PARP inhibitor 4-iodo-3-nitrobenzamide (BA) on the growth of HCC827 cells. Take P100 10 each 5 cells or at 10 per P60 4 Seed density of cells in growth medium Partition cells and incubate at 37 °C, 5% CO 2 Incubate for 12-18h. BA and the EGFR inhibitor IRESSA were added as a single dose for 72 hours. DMSO was used as a control. Cells were irradiated with 3Gy and 5Gy gamma irradiation using a gamma-irradiator Gammacell 40 Exactor (MDS Nordion, Canada). After treatment, cells were analyzed by BrdU ELISA assay (Roche Applied Science), FACS-based cell cycle assay or TUNEL.

[0333] compound

[0334] For each separate experiment BA...

Embodiment 1A

[0345] Example 1A: Combination of BA with EGFR inhibitors

[0346] The effects of BA and its nitroso metabolite (BNO) in combination with gefitinib on cell proliferation and cell cycle of the HCC827 NSLC tumor cell line were investigated.

[0347] BA and BNO were tested in the presence of gefitinib (LC Laboratories G-4408, BGF-103) as indicated in the schedule described in Table 2.

[0348] Table 2.

[0349] part

Drug (one or more)

BA

BNO

cell line

1.

EGFR inhibitors (gefitinib)

+ / -

+ / -

HCC827 non-small cell lung cancer

[0350] First, the IC50 of EGFR inhibitors against the HCC827 cell line was determined.

[0351] Second, two concentrations of BA (100 μM and 50 μM) and BNO (25 μM and 50 μM) were tested in combination with gefitinib. Gefitinib was tested in this experiment at a concentration corresponding to the IC50 of the HCC827 cell line. Compounds were simultaneously added to the cells for 72 hours.

[0...

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Abstract

In one aspect, the present invention provides a method of treating lung cancer, comprising administering to a subject at least one PARP inhibitor in combination with at least one growth factor inhibitor. In another aspect, the present invention provides a method of treating non-small cell lung cancer comprising administering to a subject at least one PARP inhibitor in combination with at least one growth factor inhibitor.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit of US Provisional Application No. 61 / 149,977, filed February 4, 2009, the disclosure of which is incorporated herein in its entirety by reference. Background of the invention [0003] Cancer is a group of diseases characterized by abnormalities in the control of cell growth. The annual incidence of cancer is estimated to exceed 1.3 million cases in the United States alone. Although cancer is treated with surgery, radiation, chemotherapy, and hormones, it remains the second leading cause of death in the United States. It is estimated that more than 560,000 Americans will die of cancer each year. [0004] Cancer cells simultaneously activate several pathways that positively and negatively regulate cell growth and cell death. This feature suggests that modulation of cell death and survival signaling could provide new strategies to improve the efficacy of current chemotherapy treatments...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A01N47/28A61K31/17
CPCA61K31/517A61K45/06A61K31/4375A61K31/17A61K31/553A61K31/4709A61K31/404A61P35/00A61P43/00A61K2300/00A61K31/167
Inventor B.M.舍曼C.布拉德利V.S.奥索夫斯卡亚
Owner BIPAR SCI INC
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