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Methods and compositions for tnbc stratification and treatment

A drug and fractional technology, applied in chemical instruments and methods, drug combinations, medical preparations containing active ingredients, etc., can solve problems such as poor treatment effect, toxic side effects, and high recurrence risk of triple-negative breast cancer

Pending Publication Date: 2020-09-11
CENT FOR EXCELLENCE IN MOLECULAR CELL SCI CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Generally, only traditional adjuvant chemotherapy or neoadjuvant chemotherapy can be used clinically, and the treatment effect is not good and has strong toxic side effects.
In addition, some chemotherapy regimens can lead to tumor resistance to the drug, making triple-negative breast cancer a higher risk of recurrence within 3 years of treatment than other subtypes of breast cancer

Method used

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  • Methods and compositions for tnbc stratification and treatment
  • Methods and compositions for tnbc stratification and treatment
  • Methods and compositions for tnbc stratification and treatment

Examples

Experimental program
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Effect test

preparation example Construction

[0237] Preparation of anti-PROCR antibody

[0238] Antibodies generally comprise two pairs of identical polypeptide chains, each pair having a full-length "light" chain (typically having a molecular weight of about 25 kDa) and a full-length "heavy" chain (typically having a molecular weight of about 50-70 kDa). The amino-terminal portion of each chain typically contains a variable region of about 100 to 110 or more amino acids that is typically responsible for antigen recognition. The carboxy-terminal portion of each chain generally defines the constant region responsible for effector function. The respective variable regions of the heavy and light chains generally exhibit the same overall structure consisting of four relatively conserved framework regions (FRs) connected by three hypervariable regions (also known as complementarity determining regions or CDRs) . The CDRs from each pair of two chains are usually aligned by the framework regions, which alignment allows bindin...

Embodiment 1

[0289] Example 1: Targeting the protein C receptor to suppress cancer stem cells in a subset of triple negative breast cancer subtypes

[0290] Breast cancer is heterogeneous, especially triple-negative breast cancer, which is composed of a variety of different molecular subgroups with unclear characteristics, and currently there are almost no targeted therapies. We recently identified protein C receptor (Procr) as a molecular marker on the surface of mammary stem cells (MaSCs). These mammary stem cells are located in the basal epithelium of the normal mammary gland. We hypothesized that TNBC is likely derived from mammary stem cells in the basal epithelium, and compared Procr in mouse and human breast cancers. In mouse mammary gland tissue, Procr is essential for mammary gland development and homeostasis maintenance. Using transplantation experiments and cell lineage tracing experiments, we found that Procr+ cells were enriched cancer stem cells (CSCs) in Wnt-1 basal-like t...

Embodiment 2

[0426] Example 2: Protein C receptors can activate multiple signaling pathways in breast cancer cells

[0427] The protein C receptor PROCR is found in various tissues as a marker of stem cells. PROCR is also involved in tumor development. However, the function of PROCR and the downstream signal transduction mechanism of PROCR are still poorly understood. Here we dissect the PROCR signaling pathway in breast cancer cells in detail. By combining protein microarray, gene knockdown and overexpression methods, we found that PROCR can simultaneously activate multiple signaling pathways. The PROCR-dependent ERK and PI3k-Akt-mTOR signaling pathways are mediated through the transactivation of Src and IGF-1R, which eventually leads to the accumulation of c-Myc and Cyclin D1 in tumors; while the PROCR-dependent RhoA-ROCK-p38 signaling pathway Activation depends on F2R. These findings were also validated by sorting primary cells in a patient-derived tumor model (PDX) of triple-negati...

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Abstract

Provided herein are methods for diagnosing and / or treating a new subtype of triple negative breast cancers (TNBC), as well as compositions and kits that can be used in such methods.

Description

technical field [0001] Provided herein are methods useful for identifying and / or treating particular subtypes of breast cancer, particularly triple negative breast cancer, as well as compositions and kits useful in such methods. Background technique [0002] Among women, breast cancer is one of the most common tumor types and is the fifth most common cause of cancer death. Due to the heterogeneity of breast cancer, the 10-year progression-free survival rate varies with the stage of breast cancer and different subtypes of breast cancer, ranging from 98% to 10%. Different types of breast cancer have significantly different biological characteristics and clinical manifestations. Therefore, the classification of breast cancer patients is an important part of deciding which treatment plan to take. For example, at present, breast cancer markers are mainly classified clinically by immunohistochemical staining and the degree of progression of breast cancer. Hormone receptors (estr...

Claims

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Application Information

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IPC IPC(8): G01N33/68G01N33/574A61K39/395C07K16/30A61P35/00
CPCC07K16/2896A61K2039/505C07K2317/22C07K2317/73C07K2317/76A61P35/00G01N33/57415G01N2333/70539A61K39/3955A61K31/337C07K2317/55C07K2317/569C07K2317/92A61K31/704A61K2300/00
Inventor 曾艺王代松
Owner CENT FOR EXCELLENCE IN MOLECULAR CELL SCI CHINESE ACAD OF SCI
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