Methods and medical uses

An endocrine therapy, subject's technology, applied in the treatment of estrogen receptor positive breast cancer combination, MPS1 inhibitor, the field of estrogen receptor positive breast cancer in subjects, can solve problems such as recurrence

Pending Publication Date: 2020-02-14
THE INST OF CANCER RES ROYAL CANCER HOSPITAL +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, not all patients will benefit from such combination therapy and many will eventually relapse due to acquired resistance

Method used

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  • Methods and medical uses
  • Methods and medical uses
  • Methods and medical uses

Examples

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Embodiment

[0885] Materials and methods

[0886] 17-β-estradiol (E2) and 4-hydroxytamoxifen (4-OHT) were purchased from Sigma-Aldrich (Dorset, UK); fulvestrant (ICI182780) was purchased from Tocris Bioscience (Bristol, UK) ; paclitaxol was purchased from Selleckchem (Suffolk, UK); palbociclib (PD-0332991) was synthesized and provided by Pfizer (Tadworth, UK). MPS1 inhibitors: CCT289346, BAY 1161909 and BAY 1217389 were synthesized and provided by ICR Cancer Therapeutics (Sutton, UK); MPS1 inhibitor NMS-P715 was purchased from Calbiochem (Hertfordshire, UK).

[0887] Tissue culture

[0888] ER+BC lines wild-type (wt) MCF7, wt-HCC1428, wt-SUM44, wt-T47D and wt-ZR75.1 cells were obtained from ATCC and incubated at 37°C in 5% CO 2 cultured in RPMI 1640 medium without phenol red (Gibco, Thermo Fisher Scientific, Loughborough, UK) supplemented with 10% fetal bovine serum (Gibco, Thermo Fisher Scientific) and 1 nM E2. Cell line identity was confirmed by short tandem repeat profiling (Promega...

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Abstract

The invention described herein provides a method for the treatment of an oestrogen receptor positive breast cancer in a subject in need thereof comprising administering to said subject a therapeutically effective amount of an MPS1 inhibitor, wherein: (i) said subject has previously been treated with an endocrine therapy; and / or (ii) said breast cancer is resistant to endocrine therapy.

Description

[0001] introduction [0002] The present invention provides new therapeutic methods and medical uses related to the treatment of endocrine resistant estrogen receptor positive breast cancer. Additionally, the present invention provides combinations useful in the treatment of estrogen receptor positive breast cancer. [0003] Background of the invention [0004] It has long been recognized that many breast cancers are hormone-dependent. Oestrogen (may be referred to interchangeably as estrogen) in particular acts as an endocrine growth factor in most breast cancers. Depriving these tumors of estrogen is therefore the main treatment modality for breast cancer. [0005] The most commonly diagnosed breast cancer (BC) in the clinic is estrogen receptor (ER) positive, and ER positive BC accounts for more than 80% of cases. [0006] Estrogen mediates its effects by binding to ER. Estrogen-binding ERs classically associate with estrogen response elements (EREs) on target genes that...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/138A61K31/437A61K31/4375A61K31/472A61K31/4725A61K31/496A61K31/4985A61K31/5025A61K31/506A61K31/517A61K31/519A61K31/52A61K31/565A61P35/00
CPCA61K31/138A61K31/437A61K31/4375A61K31/472A61K31/4725A61K31/496A61K31/4985A61K31/5025A61K31/506A61K31/517A61K31/519A61K31/52A61K31/565A61P35/00A61K2300/00
Inventor 莱斯利-安·马丁乔安娜·尼基托罗维奇-布尼亚克
Owner THE INST OF CANCER RES ROYAL CANCER HOSPITAL
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