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Combined drug for treating tumors

A drug and tumor technology, applied in the field of combined drugs for the treatment of tumors, can solve the problems of poor curative effect and easy generation of drug resistance, and achieve the effects of good clinical application prospect, excellent effect and effective treatment plan.

Active Publication Date: 2018-08-28
WEST CHINA HOSPITAL SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, after using it for a period of time, it is easy to produce drug resistance, and the curative effect in the later stage is not good.

Method used

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  • Combined drug for treating tumors
  • Combined drug for treating tumors
  • Combined drug for treating tumors

Examples

Experimental program
Comparison scheme
Effect test

experiment example 1

[0057] Experimental example 1 Inhibition of KRAS can overcome the resistance of KRAS mutant tumors to trametinib

[0058] 1. Experimental method

[0059] (1) Interfering with RAF in A549 and SW480 cells to study its effect on the expression of pERK and pMEK induced by trametinib: interfering with siRNA of CRAF or BRAF in A549 and SW480 cells, and then using 60 and 80 nM trametinib A549 and SW480 cells were treated for 48 hours, respectively. Cells were then lysed for Western blot analysis.

[0060] (2) RAF-MEK-ERK is an important cascade reaction pathway downstream of RAS. We imagine whether trametinib-induced rebound of pMEK and pERK is caused by the activation of RAS. We used pull-down to detect the activity of pan-RAS and KRAS in HCT 116, SW480 and A549 cell lines: HCT 116, A549 and SW480 cells were treated with 60 or 80 nM trametinib for 12, 24 and 48 hours, and then Perform pull-down (the steps are the same as the aforementioned Pull-down analysis), and use anti-RAS an...

Embodiment 2

[0072] Example 2 Zoledronic acid combined with trametinib

[0073] Based on the above results, we wanted to find an FDA-approved drug that could inhibit RAS activity. By reviewing the literature, we found two classes of drugs, statins and bisphosphonates. Zoledronic acid is the most extensively studied bisphosphonate, considering that zoledronic acid is used for bone metastases of clinically malignant tumors, while statins are mainly used for cardiovascular diseases, we mainly focus on zoledronic acid acid.

[0074] 1. Experimental method

[0075] (1) Efficacy of combined use of zoledronic acid and trametinib

[0076](A) Zoledronic acid (HCT 116 40μM, SW480 80μM, MDA-MB-231 12.5μM, A549 12.5μM) combined with trametinib (HCT 116 and SW480 concentration gradients were 100nM, 200nM, 400nM ; MDA-MB-231 and A549 concentration gradient is 40nM, 200nM, 1000nM) to treat four kinds of tumor cells with KRAS mutation, and use CCK8 to detect cell proliferation.

[0077] (B) Colony fo...

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Abstract

The invention discloses a combined drug for treating tumors, concretely discloses a use of an RAS inhibitor in the preparation of a drug for enhancing the KRAS mutant tumor inhibition effect of an MEKinhibitor, and also discloses a combined drug for treating KRAS mutant tumors. The combined drug for treating KRAS mutant tumors contains different specifications of unit preparations for simultaneously or separately giving an RAS inhibitor and an MEK inhibitor, and a pharmaceutically acceptable carrier. The combined drug can effectively treat the KRAS mutant tumors, has an obviously better effect than the MEK inhibitor and the RAS inhibitor used alone, and has a good clinical application prospect.

Description

technical field [0001] The invention relates to a combined drug for treating tumors. Background technique [0002] With the accelerated pace of life, the incidence of tumors is getting higher and higher, seriously threatening human life and health. KRAS mutation is the most common type of mutation in human tumors, and mutated KRAS can promote the occurrence and development of tumors by activating the RAF-MEK-ERK pathway. Since drugs that directly target KRAS have not yet been successfully developed, and drugs that target important effector molecules downstream of KRAS have not been as effective as originally thought, the prognosis of patients with KRAS mutations is very poor, and new treatment strategies are urgently needed. [0003] Trametinib (GSK1120212) is a new type of MEK inhibitor, which can inhibit the RAS downstream signaling pathway by inhibiting the MEK-ERK cascade reaction. But after it is used for a period of time, it is easy to produce the problem of drug res...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/06A61K31/519A61K31/675A61P35/00
CPCA61K31/519A61K31/675A61K45/06A61K2300/00
Inventor 毕锋夏洪伟代昕雨唐秋琳
Owner WEST CHINA HOSPITAL SICHUAN UNIV
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