Navigation Links
Some patients with treatment-resistant colorectal cancers may have a new option
Date:6/2/2013

PHILADELPHIA A subset of colorectal cancers responds to anti-epidermal growth factor receptor (anti-EGFR) therapies, but develops resistance within months. Among cancers that develop resistance to anti-EGFR therapy, some showed overexpression of a gene called MET, according to a study published in the June issue of Cancer Discovery, a journal of the American Association for Cancer Research. Preliminary data published in this study showed human tumors with MET amplification, grown in mice, responded to MET inhibitor drugs.

The MET gene is known to be amplified in about 10 percent of colorectal cancers, and is associated with worse prognosis.

The paper was also presented as part of an oral session at the 2013 American Society of Clinical Oncology Annual Meeting.

"Our studies provide evidence that colorectal cancer resistance to anti-EGFR therapies can be driven by MET gene amplification," said Alberto Bardelli, Ph.D., associate professor in the Department of Oncology at the University of Torino in Italy. "But what is more exciting is that we were able to detect these amplifications in the blood."

A subset of metastatic colorectal cancers responds to the anti-EGFR drugs cetuximab and panitumumab, but almost always develops resistance within several months of the initiation of therapy, according to Bardelli. Mutations in genes related to EGFR signaling, including KRAS, BRAF and NRAS, account for about 60 percent of the cases that develop resistance; the cause of resistance in tumors without these mutations is unknown.

"Unfortunately, patients whose tumors recur after anti-EGFR therapy are out of further options currently," said Bardelli. "The possibility that we can identify those who have MET amplification using a blood test is exciting because they might be treated with MET inhibitors."

Bardelli and his colleagues analyzed tumors from seven patients who developed resistance subsequent to anti-EGFR therapy, and identified three who did not have the previously known mutations. Using next-generation sequencing, they demonstrated amplification of the MET gene in these three tumor samples.

Blood samples collected at regular intervals during treatment with anti-EGFR therapy until relapse were available for two of the three patients. The researchers were able to detect MET amplification in the blood, and they demonstrated it occurred prior to relapse. The ability to detect MET amplification in blood provides a noninvasive, highly sensitive method for monitoring and predicting drug resistance and tumor recurrence, according to Bardelli.

Using "xenopatients" patient-derived, drug-resistant colorectal cancers grafted and grown in mice the researchers identified a novel, biologically distinct subset of tumors that were resistant to anti-EGFR drugs and did not have alterations in KRAS, BRAF or NRAS but carried MET amplification. The researchers further confirmed the overexpression of the MET gene and MET protein in these tumors using special techniques called fluorescent in situ hybridization and immunohistochemistry.

As a next step, the researchers tested the efficacy of the clinically approved MET inhibitor crizotinib in two xenopatients. According to Bardelli, a MET inhibitor in combination with an anti-EGFR drug caused maximum antitumor activity and sustained response in both xenopatients. He added that this provided proof of concept that MET inhibitors, alone or in combination with anti-EGFR therapies, offer novel therapeutic opportunities.


'/>"/>

Contact: Jeremy Moore
jeremy.moore@aacr.org
215-446-7109
American Association for Cancer Research
Source:Eurekalert

Related medicine news :

1. Therapy that heats and destroys bone tumors eases patients pain
2. Test helps target glioblastoma patients most likely to benefit from bevacizumab
3. Study finds glioblastoma patients treated with bevacizumab experience reduced cognitive function and quality of life
4. Atlanta Hearing Institute Helps Atlanta Hearing Loss Patients Both Young and Old Dramatically Improve Quality of Life
5. Dr. Richard Shuldiner, First in California to Utilize New E-Scoop Glasses, Improve Way of Life for Low Vision Patients Suffering with Macular dDegeneration (ARMD)
6. Poorer Patients Often Less Happy With Knee Replacement
7. Obese Patients May Be More Prone to Doctor Shopping
8. Foundation Recognizes Patient Navigator Jackie Glenn of The Cancer Center at Lake Manassas for Work with Breast Cancer Patients
9. Researchers narrow the search for biomarkers of drug resistance in head and neck cancer patients
10. The Lap Band Center Announces Ways for Patients to Find Out How to Lose Weight Quickly and Efficiently
11. Educated Patients Decrease Fraud and Increase Quality of Care
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:10/13/2017)... ... October 13, 2017 , ... The Visiting Nurse Association (VNA) ... a collection of specialty vendors and unique items from across the nation, this holiday-themed ... and wellness services offered by the VNA. The boutique will be open Saturday, ...
(Date:10/13/2017)... ... , ... Global Healthcare Management’s 4th Annual Kids Fun Run brought out many ... event, sponsored by Global Healthcare Management’s CEO, Jon Letko, is aimed at getting kids ... of all ages; it is a non-competitive, non-timed event, which is all about having ...
(Date:10/13/2017)... ... 13, 2017 , ... Talented host, actor Rob Lowe, is ... a new episode of "Success Files," which is an award-winning educational program broadcasted ... each subject in-depth with passion and integrity. , Sciatica occurs when the sciatic ...
(Date:10/13/2017)... ... ... “The Journey: From the Mountains to the Mission Field”: the story of a missionary ... Journey: From the Mountains to the Mission Field” is the creation of published author, ... ages and currently teaches a class of ladies at her church, which she has ...
(Date:10/12/2017)... ... October 12, 2017 , ... First Healthcare Compliance ... management, will showcase a range of technology and learning solutions at the 68th ... and Expo to be held October 14–18, 2017 at the Mandalay Bay Resort ...
Breaking Medicine News(10 mins):
(Date:9/22/2017)... Md. , Sept. 22, 2017  As the ... Republican Senators Bill Cassidy (R-LA) and ... Information notes that the medical device industry is in ... medical device tax, the 2.3% excise tax on medical ... But they also want covered patients, increased visits and ...
(Date:9/19/2017)...   ZirMed Inc ., a recognized leader in cloud-based ... has been ranked #1 by its users for the seventh ... User Survey. ZirMed was recognized as the top-ranked end-to-end revenue ... centers over 200 beds and holds one of the longest ... history. ...
(Date:9/13/2017)... ATLANTA , Sept. 13, 2017   OrthoAtlanta ... to the Atlanta Football Host Committee (AFHC) for the 2018 ... Monday, Jan. 8, 2018, at Mercedes-Benz Stadium in ... part of the AFHC "I,m In" campaign, participating in many ... ...
Breaking Medicine Technology: