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TARGETING ACTIVATED MET FOR TREATING CANCERS RESISTANT TO ANTI-ERBB THERAPEUTICS

Technology Benefits

Lung Cancer; ErbB driven tumors; Drug Resistance

Technology Application

Development of rapid assays (in form of kits) to screen for MET activation in tumors from cancer patients that undergo or will be subject to anti-ErbB therapy, or developed resistance to such treatment.

Detailed Technology Description

Tumors driven by ErbB (eg. EGFR) receptor tyrosine kinase pathway activation initially respond to antagonists but eventually develop resistance. One way for cancer cells to escape treatment is to elaborate other signaling pathways for their survival. The invention is based on analysis of non-small cell lung cancer cell (NSCCL) clones that became resistant after prolonged treatment with EGFR inhibitors. A focal amplification of MET proto-oncogene with subsequent activation of ErbB3/PI3K was discovered in these resistant clones. Similar, MET amplification was identified in 22% lung cancer specimens from human patients that developed resistance to anti-EGFR therapy. Inhibition of MET restores sensitivity of resistant cells to EGFR antagonists. The combined therapy with MET and EGFR pathway inhibitors will be a treatment of choice for such tumors.

Supplementary Information

Inventor: LOOK, A., Thomas | SIDI, Samuel
Priority Number: WO2009099601A3
IPC Current: G01N0033574
Assignee Applicant: Dana-Farber Cancer Institute Inc.
Title: CHK1 SUPPRESSES A CASPASE-2 APOPTOTIC RESPONSE TO DNA DAMAGE THAT BYPASSES P53, BCL-2 AND CASPASE-3 | CHK1 SUPPRIME UNE RÉPONSE APOPTOTIQUE DE LA CASPASE-2 FACE AUX LÉSIONS DE L'ADN QUI COURT-CIRCUITE P53, BCL-2 ET LA CASPASE-3
Usefulness: CHK1 SUPPRESSES A CASPASE-2 APOPTOTIC RESPONSE TO DNA DAMAGE THAT BYPASSES P53, BCL-2 AND CASPASE-3 | CHK1 SUPPRIME UNE RÉPONSE APOPTOTIQUE DE LA CASPASE-2 FACE AUX LÉSIONS DE L'ADN QUI COURT-CIRCUITE P53, BCL-2 ET LA CASPASE-3
Summary: The methods are useful for determining whether a subject having a cancer is a candidate for a Chk1 inhibitor-based cancer treatment regimen, for determining a course of cancer treatment regimen, for monitoring effectiveness of a Chk1 inhibitor-based cancer treatment regimen, and for treating a cancer (all claimed). Cancer includes, but is not limited to: sarcoma, myxoma, rhabdomyoma, fibroma, lipoma and teratoma.
Novelty: Determining whether a subject having a cancer is a candidate for a Csk homologous kinase (Chk)1 inhibitor-based cancer treatment regimen comprises determining caspase-2 activation in the test cancer cells contacted with Chk1 inhibitor

Industry

Disease Diagnostic/Treatment

Sub Category

Cancer/Tumor

*Abstract

Development of rapid assays (in form of kits) to screen for MET activation in tumors from cancer patients that undergo or will be subject to anti-ErbB therapy, or developed resistance to such treatment.

Country/Region

USA