Navigation Links
Some patients with treatment-resistant colorectal cancers may have a new option

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
American Association for Cancer Research

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:
(Date:6/26/2016)... ... June 26, 2016 , ... On June 10-11, 2016, A ... 2016 Cereal Festival and World’s Longest Breakfast Table in Battle Creek, MI, where the ... history as home to some of the world’s leading providers of cereal and other ...
(Date:6/25/2016)... , ... June 25, 2016 , ... ... policy issues and applications at AcademyHealth’s Annual Research Meeting June 26-28, 2016, at ... on several important health care topics including advance care planning, healthcare costs and ...
(Date:6/25/2016)... ... 25, 2016 , ... As a lifelong Southern Californian, Dr. Omkar Marathe earned ... the David Geffen School of Medicine at UCLA. He trained in Internal Medicine at ... fellowship in hematology/oncology at the UCLA-Olive View-Cedars Sinai program where he had the opportunity ...
(Date:6/24/2016)... ... June 24, 2016 , ... Those who have experienced traumatic events may suffer ... unhealthy avenues, such as drug or alcohol abuse, as a coping mechanism. To avoid ... healthy coping following a traumatic event. , Trauma sufferers tend to feel a range ...
(Date:6/24/2016)... , ... June 24, 2016 , ... ... offering micro-osteoperforation for accelerated orthodontic treatment. Dr. Cheng has extensive experience with all ... brackets , AcceleDent, and accelerated osteogenic orthodontics. , Micro-osteoperforation is a revolutionary ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... -- Research and Markets has announced the addition ... report to their offering. ... The World Market for Companion Diagnostics covers the world ... in the report includes the following: , ... by Region (N. America, EU, ROW), 2015-2020 , World ...
(Date:6/24/2016)... 2016   Pulmatrix, Inc ., (NASDAQ: ... drugs, announced today that it was added to the ... its comprehensive set of U.S. and global equity indexes ... important milestone for Pulmatrix," said Chief Executive Officer ... our progress in developing drugs for crucial unmet medical ...
(Date:6/24/2016)... KNOXVILLE, Tenn. , June 24, 2016 /PRNewswire/ ... market providing less invasive and more durable cerebrospinal ... million in funding.  The Series-A funding is led ... the Lighthouse Fund, and other private investors.  Arkis, ... less-invasive neurosurgical instrumentation and the market release of ...
Breaking Medicine Technology: