Navigation Links
Study points to strategy for overcoming resistance to targeted cancer drug
Date:9/7/2011

BOSTON -- Scientists at Dana-Farber Cancer Institute and colleagues overseas have discovered a pair of backup circuits in cancer cells that enable the cells to dodge the effect of a widely used cancer drug. Jamming those circuits with targeted therapies may heighten or restore the drug's potency, according to a study published in the Sept. 7 issue of Science Translational Medicine.

The research focused on the drug cetuximab, an antibody that interferes with cancer cell growth by blocking a structure known as the epidermal growth factor receptor (EGFR). Cetuximab is effective in many patients with colorectal cancer or squamous cell cancer of the head and neck, but the benefits rarely last longer than a year, and some patients receive no benefit from the drug.

Until now, scientists haven't known why cancers that initially respond to cetuximab become resistant to it, or how to overcome such resistance.

In the new study, researchers led by Pasi Janne, MD, PhD, of Dana-Farber and Kimio Yonesaka, MD, PhD, formerly of Dana-Farber and now at Kinki University School of Medicine, in Osaka, Japan, found that in some cetuximab-resistant cancer cells, a protein known as ERBB2 was actively sending "grow" signals, circumventing the "stop growing" signals triggered by cetuximab. The researchers discovered that ERBB2's activity sprang from an oversupply of the protein's parent gene, Her2/neu, or by a related protein, ERBB3, when prompted by high levels of the protein heregulin. In both cases, the new growth messages are unaffected by cetuximab.

"ERBB2 activates a critical signaling pathway that is not normally blocked by cetuximab, and in this way subverts cetuximab's function," says Janne, the study's co-senior author with Kazuhiko Nakagawa, MD, PhD, of Kinki University. "Because ERBB2 isn't affected by cetuximab, this is an easy way for cancers to become resistant to the drug."

The findings suggest that combining cetuximab with ERBB2-inhibiting drugs could be an effective therapy for cancers that are cetuximab-resistant from the start or for those that become resistant over time, the study authors say. Several such inhibitors have already been approved, while others are undergoing clinical study.

"We hope the findings of our study will inspire the development of clinical trials aimed at overcoming cetuximab resistance," Yonesaka remarks. "We've identified biomarkers that can be used to select cetuximab-resistant patients who may benefit from a combination of cetuximab and ERBB2 inhibitors."

Janne estimates that up to 40 percent of colorectal cancers are cetuximab-resistant when first diagnosed. He notes that although the ERBB2 pathway may be responsible for many cases of cetuximab resistance, there are undoubtedly other pathways, yet to be discovered, that play a similar role. Further research is needed to confirm ERBB2's role in cetuximab resistance and to develop strategies for testing ERBB2 inhibitors and cetuximab in clinical trials.


'/>"/>

Contact: Bill Schaller
william_schaller@dfci.harvard.edu
617-632-5357
Dana-Farber Cancer Institute
Source:Eurekalert  

Related medicine news :

1. Despite Treatment, Employees with Depression Generate Higher Absentee Costs, According to Thomson Reuters Study
2. American Council on Exercise (ACE) Study Reveals Kettlebells Provide Powerful Workout in Short Amount of Time
3. TV drama can be more persuasive than news program, study finds
4. Study carried out into biological risks of eating reptiles
5. Neuroimaging study may pave way for effective Alzheimers treatments
6. Study finds racial gaps continue in heart disease awareness
7. Luth Researchs IndicatorEDG(TM) Study Finds Americans Hopes of Achieving Their Dreams Are Fading
8. First blinded study of venous insufficiency prevalence in MS shows promising results
9. Soothing infants with food focus of childhood obesity study
10. People with anxiety disorder less able to regulate response to negative emotions, study shows
11. American Heart Association Rapid Access Journal Report: Study Finds Racial Gaps Continue in Heart Disease Awareness, Low Knowledge of Heart Attack Warning Signs Among Women
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Study points to strategy for overcoming resistance to targeted cancer drug
(Date:6/25/2016)... ... ... temporary closing of Bruton Memorial Library on June 21 due to a possible lice infestation, ... aspect of head lice: the parasite’s ability to live away from a human host, and ... necessary one in the event that lice have simply gotten out of control. , As ...
(Date:6/25/2016)... ... 25, 2016 , ... On Friday, June 10, Van Mitchell, Secretary of the ... to iHire in recognition of their exemplary accomplishments in worksite health promotion. , The ... Health & Wellness Symposium at the BWI Marriott in Linthicum Heights. iHire was one ...
(Date:6/24/2016)... CA (PRWEB) , ... June 24, 2016 , ... Marcy was in a crisis. Her ... would lash out at his family verbally and physically. , “When something upset him, he ... he would use it. He would throw rocks at my other children and say he ...
(Date:6/24/2016)... ... ... Topical BioMedics, Inc, makers of Topricin and MyPainAway Pain Relief Products, join The ‘Business for ... $12 an hour by 2020 and then adjusting it yearly to increase at the same ... wage, assure the wage floor does not erode again, and make future increases more predictable. ...
(Date:6/24/2016)... ... 2016 , ... Strategic Capital Partners, LLC (SCP) in concert ... capital for emerging technology companies. SCP has delivered investment events and professional ... than a million dollars of capital investment for five companies. The ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... SAN CLEMENTE, Calif. , June 24, 2016 /PRNewswire/ ... pulmonary function testing company, is now able to perform sophisticated lung ... ndd Medical Technologies , Inc. Patients are ... labs.  Thanks to ndd,s EasyOne PRO ® , ARL patients like ... any needed testing done in the comfort of her own home. ...
(Date:6/24/2016)... Mass. , June 24, 2016   Pulmatrix, ... pharmaceutical company developing innovative inhaled drugs, announced today that ... Russell Investments reconstituted its comprehensive set of ... "This is an important milestone for Pulmatrix," ... will increase shareholder awareness of our progress in developing ...
(Date:6/23/2016)... June 23, 2016  MedSource announced today that ... e-clinical software solution of choice.  This latest decision ... value to their clients by offering a state-of-the-art ... relationship establishes nowEDC as the EDC platform of ... full-service clients.  "nowEDC has long been a preferred ...
Breaking Medicine Technology: