Type

Journal Article

Authors

Alex J Eustace
Bryan T Hennessy
Stephen F Madden
Sinead Toomey
Ann M Hopkins
Sri H Velanki
Aoife Carr
John O'Shea
Clare Morgan
Mattia Cremona
and 1 others

Subjects

Biochemistry

Topics
gene apoptosis therapeutic cell lines proteins strategy development erbb phase

Development of a personalized therapeutic strategy for ERBB-gene-mutated cancers. (2017)

Abstract The application of genomic technologies to patient tumor samples identified groups of signaling pathways which acquire activating mutations. Some cancers are dependent on these mutations and the aberrant proteins resulting from these mutations can be targeted by novel drugs which can eradicate the cancer. We used www.cbioportal.org to determine the frequency of ERBB mutations in solid tumors. We then determined the sensitivity of a panel of cell lines to clinically available PI3K inhibitors. Using proliferation and apoptosis assays as well as functional interrogation with reverse phase protein arrays we demonstrated the impact of targeting ERBB-mutant cancers with the combination of a PI3K inhibitor and the pan-HER family inhibitor afatinib. In over 14,000 patients we found that 12% of their tumors have an ERBB family gene mutation (EGFR, ERBB2, ERBB3 and ERBB4). In cancers not commonly associated with HER family protein overexpression, such as ovarian, endometrial, melanoma and head and neck cancers ( We demonstrate that ERBB family mutations are common in cancers not associated with overexpression or amplification of HER family proteins. These ERBB family mutant cancers are sensitive to treatment with PI3K inhibitors, and when combined with pan-HER inhibitors have synergistic antiproliferative effects.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Alex J Eustace, Bryan T Hennessy, Stephen F Madden, Sinead Toomey, Ann M Hopkins, Sri H Velanki, Aoife Carr, John O'Shea, Clare Morgan, Mattia Cremona and 1 others

Experts in our system

1
Alex J Eustace
Dublin City University
 
2
Bryan T Hennessy
Royal College of Surgeons in Ireland
Total Publications: 33
 
3
Stephen F Madden
Dublin City University
Total Publications: 45
 
4
Sinead Toomey
Royal College of Surgeons in Ireland
Total Publications: 26
 
5
Ann M Hopkins
Royal College of Surgeons in Ireland
Total Publications: 26
 
6
Aoife Carr
Royal College of Surgeons in Ireland
Total Publications: 8
 
7
Clare Morgan
Royal College of Surgeons in Ireland
Total Publications: 9
 
8
Mattia Cremona
Royal College of Surgeons in Ireland
Total Publications: 11