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A method for predicting responsiveness to a treatment with an EGFR inhibitor

An inhibitor and prognostic technology, applied in biochemical equipment and methods, microbial measurement/testing, drug combination, etc., can solve problems such as undisclosed cancer patients

Inactive Publication Date: 2016-07-13
INTEGRAGEN
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there is no disclosure of its association with whether cancer patients are able to respond to EGFR inhibitors

Method used

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  • A method for predicting responsiveness to a treatment with an EGFR inhibitor
  • A method for predicting responsiveness to a treatment with an EGFR inhibitor
  • A method for predicting responsiveness to a treatment with an EGFR inhibitor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0181] Example 1: DBNDD2 and EPB41L4B are targets of hsa-miR-31-3p and independently predict EGFR inhibitor response

[0182] patients and methods

[0183] patient

[0184] Twenty mCRC (metastatic colorectal cancer) patients constituted the patient group, 14 males and 6 females. The median age was 66.49±11.9 years old. All patients received the combination of irinotecan and cetuximab. Chemotherapy drugs recorded prior to the introduction of cetuximab belonged to the number of chemotherapy lines. The median follow-up until progression was 20 weeks, and the median overall survival was 10 months. All samples were from resections and fixed in formalin and paraffin embedded (FFPE).

[0185] Cell Culture and Transfection

[0186] We selected 3 colorectal adenocarcinoma cell lines weakly expressing hsa-miR-31-3p from the American Type Culture Collection (ATCC, Manassas, CA): HTB-37, CCL-222 and CCL-220 -1. HTB-37 was maintained in Dulbecco's Modified Eagle's Medium (DMEM)...

Embodiment 2

[0208] Example 2: Creation of a Tool Using DBNDD2 and EPB41L4B Expression to Predict Response to EGFR Inhibitors

[0209] patients and methods

[0210] patient

[0211] Twenty mCRC patients constituted the patient group (13 males, 7 females). The median age was 67±11.2 years old. All had metastatic disease at enrollment. All of these patients had KRAS wild-type metastatic colon cancer. All patients were considered refractory to 5-fluorouracil-based regimens in combination with irinotecan and oxaliplatin. They received anti-EGFR-based chemotherapy, panitumumab in 8 patients, cetuximab in 10 patients, and a combination of panitumumab and cetuximab in 2 patients. Chemotherapy drugs recorded before the introduction of cetuximab and panitumumab belonged to the few-line drugs. The median follow-up until progression was 21 weeks, and the median overall survival was 8.9 months.

[0212] Measurement of Gene Expression

[0213] qRT-PCR for the expression of DBNDD2 and EPB41L...

Embodiment 3

[0220] Example 3: Replication of the predictive value of DBNDD2 and EPB41L4B for EGFR inhibitors in a new and independent population

[0221] patients and methods

[0222] patient

[0223] Forty-two mCRC (metastatic colorectal cancer) patients constituted the patient group, 27 males and 15 females. The median age was 59±12.1 years old. All had metastatic disease at enrollment. Based on the protocol, all patients were treated with third-line therapy with irinotecan and panitumumab after progression on chemotherapy with oxaliplatin and irinotecan. The median follow-up until progression was 23 weeks, and the median overall survival was 9.6 months. Twenty-six samples were provided as FFPE and 16 as frozen tissue.

[0224] Measurement of Gene Expression

[0225] qRT-PCR validation of target expression from frozen or FFPE patient samples was performed with 20 ng of total RNA using the ABI7900HT Real-Time PCR System (Applied Biosystem). All reactions were performed in trip...

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Abstract

The present invention relates to a method for predicting whether a patient with a cancer is likely to respond to an epidermal growth factor receptor (EGFR) inhibitor, which method comprises determining the expression level of at least one target gene of hsa-miR-31 -3p (SEQ ID NO:1 ) miRNA in a sample of said patient, wherein said target gene of hsa-miR-31 -3p is selected from DBNDD2 and EPB41 L4B. The invention also relates to kits for measuring the expression of DBNDD2 and / or EPB41 L4B and at least one other parameter positively or negatively correlated to response to EGFR inhibitors. The invention also relates to therapeutic uses of an EGFR inhibitor in a patient predicted to respond to said EGFR inhibitor.

Description

technical field [0001] The present invention provides a method of individualizing chemotherapy for cancer treatment, in particular a method of evaluating a patient's responsiveness to one or more epidermal growth factor receptor (EGFR) inhibitors prior to treatment with such agents, based on The expression level of at least one target gene of hsa-miR-31-3p (SEQ ID NO: 1) miRNA is determined, wherein the target gene of hsa-miR-31-3p is selected from DBNDD2 and EPB41L4B. Background technique [0002] The epidermal growth factor receptor (EGFR) pathway plays a key role in the initiation and progression of human epithelial cell carcinoma. In diverse human cancer cells with functional EGFR-dependent autocrine growth pathways, combination therapy with EGFR inhibitors has synergistic growth inhibitory and proapoptotic activities, leading to more efficient and sustained inhibition of Akt. [0003] EGFR inhibitors have been approved or tested in the treatment of various cancers, inc...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/68
CPCC12Q2600/106C12Q2600/158C12Q1/6886A61P35/00C12Q2600/178
Inventor R·蒂埃博
Owner INTEGRAGEN
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