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MEK1 Mutation Conferring Resistance to RAF and MEK Inhibitors

a technology of mek1 and raf, which is applied in the field of mek1 mutation conferring resistance to raf and mek inhibitors, can solve the problems that the given chemotherapeutic agent can become ineffective in certain individuals

Inactive Publication Date: 2013-06-06
DANA FARBER CANCER INST INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention is about a mutation in a protein called MEK1 that makes cancer cells resistant to chemotherapy. This mutation was detected and can be used to identify cancer patients who may be resistant to treatment. It also allows for the development of new treatments using second-generation MEK inhibitors that are effective against this mutated protein. This innovation can be particularly useful in treating cancer.

Problems solved by technology

As a result, a given chemotherapeutic agent can become ineffective in certain individuals.

Method used

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  • MEK1 Mutation Conferring Resistance to RAF and MEK Inhibitors
  • MEK1 Mutation Conferring Resistance to RAF and MEK Inhibitors
  • MEK1 Mutation Conferring Resistance to RAF and MEK Inhibitors

Examples

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example 1

Identification of Activating MEK1 C121S Mutation

[0230]In this example, DNA samples from a patient with metastatic melanoma who developed resistance to the BRAF inhibitor PLX4032 were used to identify an activating MEK1 mutation that conferred resistance to both BRAF and MEK1 inhibitors. More specifically, massively parallel sequencing was used to conduct a comparative genomic analysis of 3 different DNA samples from the patient: (i) tumor that was sensitive to PLX4032, (ii) tumor that was resistant to PLX4032, and (iii) normal skin, to thereby allow for the identification of the activating MEK1 mutation.

[0231]The patient was a 38 year old man who was diagnosed with metastatic melanoma in February 2009. He initially presented with a mass in his right axilla, and a staging PET-CT demonstrated a large lesion in the right latissimus dorsi as well as multiple hypermetabolic foci in the lungs, liver, bones and several subcutaneous sites. Biopsy of the latissimus dorsi mass showed malignan...

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Abstract

Nucleic acids and proteins having a mutant MEK sequence, and methods concerning identification of patients having resistance to treatment with anti-cancer agents, specifically inhibitors of RAF or MEK are provided. Methods of treatment and for optimizing treatment for patients having a mutation in a MEK1 sequence are also provided.

Description

RELATED APPLICATIONS[0001]This application claims the benefit of the filing date under 35 U.S.C. §119(e) of Provisional U.S. Patent Application Ser. No. 61 / 352,959, filed Jun. 9, 2010, which is incorporated by reference in its entirety.FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT[0002]This invention was made with government support under federal grant number K08 CA115927 awarded by National Institutes of Health. The government has certain rights in the invention.BACKGROUND OF THE INVENTION[0003]The treatment of cancer is one of the greatest challenges in modern medicine. While chemotherapeutic agents are typically an effective means of treating or reducing the symptoms associated with cancer, in some cases, resistance to one or more chemotherapeutic agents manifests during treatment. As a result, a given chemotherapeutic agent can become ineffective in certain individuals. The molecular mechanisms responsible for the development of resistance in various types of cancer are poorly und...

Claims

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Application Information

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IPC IPC(8): A61K31/4745C07H21/04C12N9/12C12Q1/68
CPCC12N9/1205C12Q1/6886C12Y207/12002C12Q2600/136C12Q2600/156C12Q2600/106A61P35/00A61P35/02A61P35/04C12N15/63A61K38/005C12N15/1003C12Q1/6809C12Q1/6827C12Q1/686G01N33/5743G01N2333/91205G01N2500/10G01N2500/20
Inventor GARRAWAY, LEVI A.EMERY, CAROLINEWAGLE, NIKHIL
Owner DANA FARBER CANCER INST INC