In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. e21068-e21068
Abstract:
e21068 Background: The human EGF receptor family (HER’s) consists of two clinically validated drug targets (EGFR and HER2), and two receptors (HER3 and HER4) which are the subject of intensive preclinical and early clinical investigation. Although drugs inhibiting both EGFR and HER2 show significant antitumor activity in the clinic, the acquisition of resistance is a hallmark of these and other targeted therapies. In the case of both targets, one of the emerging resistance mechanisms is the co-expression of other receptor tyrosine kinases, including members of the EGFR superfamily, cMet and IGF1R. As an example, it was recently shown that HER2 co-expression mediates resistance in cetuximab treated head and neck cancer. Similarly, much attention has been paid to HER3 both as a bona fide drug target and a resistance mechanism. Methods: Using trypsin digestion mapping of recombinant proteins, we identified unique peptide sequences from each of these receptors, and built quantitative mass spectrometric (MS) assays which could be multiplexed into a single MS analysis of 1ug of tumor protein. Assays were preclinically validated on 10 formalin fixed cell lines, and FFPE human NSCLC primary tumor xenografts. Results: The validated multiplex assay was used to measure expression levels of HER1-3, cMET and IGF1R in two cohorts of clinical tumor tissue which had been treated with HER family antagonists. One, a set of gefitinib treated NSCLC tumors (N=15) , and a second, a cohort of advanced breast cancer tissues which had adjuvant treatment with trastuzumab(N=18). Here we present expression patterns for each of the RTKs studied, with the intent to begin to define the relationship between RTK expression and response to either gefitinib or trastuzumab treatment. Conclusions: It is important to not only understand primary mechanisms of tumor growth, but also mechanisms of resistance in patients undergoing targeted therapies. Our Liquid Tissue-SRM promises to be a platform which can deliver extremely high sensitivity, absolute specificity as well as multiplexing capabilities to assess critical oncology targets.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2012.30.15_suppl.e21068
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2012
detail.hit.zdb_id:
2005181-5
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