Methods of treating cancer patients with farnesyl transferase inhibitors

A farnesyltransferase and inhibitor technology, applied in the fields of molecular biology and cancer biology, can solve problems such as different responses of patients

Inactive Publication Date: 2018-08-07
KURA ONCOLOGY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, patients respond differently to FTI therapy

Method used

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  • Methods of treating cancer patients with farnesyl transferase inhibitors
  • Methods of treating cancer patients with farnesyl transferase inhibitors
  • Methods of treating cancer patients with farnesyl transferase inhibitors

Examples

Experimental program
Comparison scheme
Effect test

Embodiment I

[0752] Identification of immunological biomarkers related to the clinical benefit of tipifarnib

[0753] The analysis of gene expression distribution in bone marrow samples from two AML studies and the IC50 data of tipifarnib in multiple cell lines showed that a variety of immune-related genes, especially NK cell-related genes, are better than tipifarnib. Prognosis is relevant. Although some of these genes do not appear to be specific for tipifarnib treatment, other genes including KIR2DS2, KIR2DL2, KIR2DS5, KIR2DL5, and GZMM are specifically related to the clinical benefit of tipifarnib and not with other non-FTI chemotherapy Reagents such as cytarabine and mitoxantrone are related.

[0754] The current study used microarray data generated by global gene expression analysis of bone marrow samples collected in two clinical studies investigating the efficacy and safety of FTI Tipifarnib. One clinical study was conducted in adult patients over 65 years of age with previously untre...

Embodiment II

[0779] A. Stratification of AML patients in clinical trials of Tipifarnib.

[0780] Clinical trials can be conducted, which include KIR classification as part of the patient inclusion indicators. For example, research on the treatment of tipifarnib can be conducted in AML patients who are older than 60 years of age or who are not suitable for standard chemotherapy, or who have refractory or relapsed AML.

[0781] Before the AML patient enters the clinical trial, a bone marrow sample or blood sample is obtained from the patient. The sample is then subjected to microarray analysis. DNA was isolated from Trizol-treated bone marrow samples according to the manufacturer's instructions (Qiagen). Analyze the global gene expression of samples and quantitative polymerase chain reaction (QPCR) of specific genes, including KIR2DS2, KIR2DL2, KIR2DS5 and KIR2DL5. In addition, microarray analysis provides the genotype of the patient's KIR gene. If the patient is identified as a carrier of t...

Embodiment III

[0801] Individualized treatment judgment for CMML patients

[0802] The following process can be used to determine whether CMML patients are suitable for FTI treatment, for example, tipifarnib treatment.

[0803] Samples of BM were collected from patients before treatment, and monocytes were processed in situ. Total RNA was extracted from cell samples using Trizol kit (Qiagen, Santa Clarita, CA). The RNA quality was determined by evaluating the presence of ribosomal bands on an Agilent Bioanalyzer (Agilent, Palo Alto, CA). Good quality samples are further processed for microarray analysis.

[0804] For each sample, 1 g of total RNA (determined by OD260) was reverse transcribed using High Capacity cDNA Reverse Transcription kit (Applied Biosystems, Foster City, CA) according to the manufacturer's instructions. The sample can then be incubated at 25°C for 10 minutes and then at 37°C for 30 minutes for optimal RNA conversion. QPCR was performed using ABI Prism 7900HT Sequence Detec...

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Abstract

The present invention relates to the field of molecular biology and cancer biology. Specifically, the present invention relates to methods of treating a subject with a farnesyltransferase inhibitor (FTI) that include determining whether the subject is likely to be responsive to the FTI treatment based on genotyping and expression profiling of certain immunological genes and RAS mutation status inthe subject.

Description

[0001] This application is a division of the invention application with the filing date of August 16, 2016, the application number of 201680031764.4, and the title of "Methods for using farnesyltransferase inhibitors to treat cancer patients". Technical field [0002] The present invention relates to the fields of molecular biology and cancer biology. This article provides methods to use certain immune-related genes as biomarkers to predict the clinical sensitivity and response to farnesyltransferase inhibitor therapy in subjects with cancer. Further provided herein are kits for performing these methods. Background of the invention [0003] The stratification of patient populations to improve treatment response rates is increasingly valuable in the clinical management of cancer patients. Farnesyl transferase inhibitors (FTI) are useful therapeutic agents in the treatment of cancers such as leukemia, lymphoma and certain solid tumors. However, patients respond differently to FTI ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61K31/4709A61P35/00C12Q1/6886
CPCA61K45/00A61P35/00C12Q1/6886A61P35/04A61P35/02C12Q2600/106C12Q2600/156C12Q2600/158A61K31/4709A61P43/00A61K31/4725A61K45/06
Inventor 安东尼奥·瓜尔贝托凯瑟琳·罗斯·肖尔兹
Owner KURA ONCOLOGY
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