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Methods and compositions for enhancing cancer therapy

A therapy, cancer technology, applied in the field of enhanced cancer therapy and composition, able to solve problems such as disease recurrence

Inactive Publication Date: 2017-08-18
THE SCRIPPS RES INST
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The main underlying problem is that some tumor cells are treatment resistant and many develop treatment resistance, leading to disease relapse, often years after apparently successful initial adjuvant therapy

Method used

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  • Methods and compositions for enhancing cancer therapy
  • Methods and compositions for enhancing cancer therapy
  • Methods and compositions for enhancing cancer therapy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0109] Example 1 Metabolic Pathways Affecting Cancer Therapy Efficacy and Resistance

[0110] To better understand the mechanisms driving tumor development and cancer progression, we analyzed cellular energy metabolism in breast cancer cells. due to NAD + We are particularly interested in the possible role of synthetic and salvage pathways in tumor progression and therapy resistance. We identify specific metabolic pathways that influence therapy efficacy and the development of resistance to major types of breast cancer treatments.

[0111] To directly analyze the effect of NAMPT expression on the responsiveness of ER-positive breast cancer cells to antihormonal therapy, we investigated the response to tamoxifen, a widely used ER antagonist through its active metabolite 4-hydroxytamoxifen. Moxifen effect), whether and how the regulation of NAMPT expression affects tumor cells. To this end, we first measured NAMPT expression in MCF7 and T47D cells, both of which are luminal e...

Embodiment 2

[0113] Example 2 Enhances antihormonal therapy by upregulating the NAMPT pathway

[0114] The results described in Example 1 were completely unexpected, as they were contrary to what was suggested in the literature (e.g., Hsu et al., Autophagy 5, 1229-1231, 2009), and our own previous studies showed that nicotinamide induced Phagocytosis (Santidrian et al., J. Clin. Invest. 123:1068-1081, 2013), a mechanism thought to suppress the effects of stress-induced anticancer treatments, including antihormonal therapy. The results described in Example 1 further suggest that activation of the NAMPT pathway can enhance resistance to hormone therapy in ER-positive breast cancer cells.

[0115] To further analyze this clinically highly relevant finding indicative of a potential new therapeutic approach, we compared tamoxifen treatment of estrogen-positive MCF7 and T47D breast cancer cells with NAM (vitamin B3 and NAD + precursor) processing combination. Such as Figure 4 As shown in A. ...

Embodiment 3

[0120] Example 3 Prediction or Diagnosis of the Efficacy of Antihormonal Therapy

[0121] The unexpected results observed by the inventors further suggest that NAMPT expression in breast cancer can be used as a biomarker to monitor the efficacy of anti-hormone therapy and to determine the probability of tumor recurrence after anti-hormone therapy. To examine the clinical evidence for this possibility, we analyzed whether NAMPT expression was associated with antihormonal therapy outcome. We used publicly available clinical databases to investigate the relationship between NAMPT expression and prognosis in ER-positive breast cancer patients ( Figure 10 with 11 ). Results from 1881 breast cancer patients (Ringnér et al., PLoS One 6, e17911, 2011) showed that ER-positive breast cancers had significantly lower NAMPT expression levels than ER-negative breast cancers ( figure 2 ). Interestingly, our analysis further revealed that ER-positive breast cancers comprise a subgroup i...

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Abstract

The present invention provides methods and compositions for enhancing efficacy of anti-hormone treatment, or for preventing cancer relapse or progression following treatment. The invention also provides methods for re-sensitizing or sensitizing treatment resistant cancer cells or patients with treatment-refractory cancer cells to continuing or starting anti-hormone treatment. Further provided in the invention are methods for prognosis or diagnosis of anti-hormone treatment effect or likelihood of cancer relapse or metastasis following anti-hormone treatment.

Description

[0001] Cross References to Related Applications [0002] The subject patent application claims the benefit of priority from US Provisional Patent Application No. 62 / 025,596 (filed July 17, 2014). The entire disclosure of the priority application is hereby incorporated by reference in its entirety for all purposes. [0003] Statement of Government Funding [0004] This invention was made with United States Government support under Grant No. R01CA170737 and Grant No. R01CA170140 awarded by the National Institutes of Health. The US Government has certain rights in this invention. Background technique [0005] Cancer is one of the leading causes of death, and metastatic cancer is often incurable. For example, breast cancer metastasis to lung, liver, bone and brain is the leading cause of death in breast cancer patients. This involves dissemination of cancer cells through the bloodstream and lymphatic system, and depends on both adhesive and invasive tumor cell functions and th...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/7084A61P35/00C07H19/207
CPCA61K31/405A61K31/706A61K31/7088A61K45/06A61K48/005G01N33/5735G01N33/57415G01N33/57449G01N33/57484G01N2333/91142G01N2800/52A61K31/455A61K38/45C12N9/1077C12Y204/02012A61P15/00A61P35/00A61K48/00C12Q1/48G01N33/574
Inventor 安东尼奥·费尔南德斯·桑蒂德里安布伦希尔德·H·费尔丁
Owner THE SCRIPPS RES INST
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