Back to Search
Start Over
Src, a potential target for overcoming trastuzumab resistance in HER2-positive breast carcinoma
- Source :
- BRITISH JOURNAL OF CANCER, r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau, instname, British Journal of Cancer
- Publication Year :
- 2014
- Publisher :
- NATURE PUBLISHING GROUP, 2014.
-
Abstract
- Background: Src is a non-receptor tyrosine kinase involved in signalling and crosstalk between growth-promoting pathways. We aim to investigate the relationship of active Src in response to trastuzumab of HER2-positive breast carcinomas. Methods: We selected 278 HER2-positive breast cancer patients with (n = 154) and without (n = 124) trastuzumab treatment. We performed immunohistochemistry on paraffin-embedded tissue microarrays of active Src and several proteins involved in the PI3K/Akt/mTOR pathway, PIK3CA mutational analysis and in vitro studies (SKBR3 and BT474 cancer cells). The results were correlated with clinicopathological factors and patients' outcome. Results: Increased pSrc-Y416 was demonstrated in trastuzumab-resistant cells and in 37.8% of tumours that correlated positively with tumour size, necrosis, mitosis, metastasis to the central nervous system, p53 overexpression and MAPK activation but inversely with EGFR and p27. Univariate analyses showed an association of increased active Src with shorter survival in patients at early stage with HER2/hormone receptor-negative tumours treated with trastuzumab. Conclusions: Src activation participates in trastuzumab mechanisms of resistance and indicates poor prognosis, mainly in HER2/hormone receptor-negative breast cancer. Therefore, blocking this axis may be beneficial in those patients.
- Subjects :
- Adult
Cancer Research
Class I Phosphatidylinositol 3-Kinases
Receptor, ErbB-2
DNA Mutational Analysis
Antineoplastic Agents
Breast Neoplasms
Kaplan-Meier Estimate
Biology
Antibodies, Monoclonal, Humanized
Metastasis
Central Nervous System Neoplasms
Phosphatidylinositol 3-Kinases
Breast cancer
Trastuzumab
Cell Line, Tumor
HER2 breast carcinoma
PTEN/PI3K/Akt
medicine
Humans
Molecular Targeted Therapy
skin and connective tissue diseases
neoplasms
PI3K/AKT/mTOR pathway
Aged
Aged, 80 and over
Middle Aged
medicine.disease
MAPK
Enzyme Activation
src-Family Kinases
Oncology
trastuzumab resistance
Chemotherapy, Adjuvant
Drug Resistance, Neoplasm
Cancer cell
Cancer research
Female
HER2 Positive Breast Carcinoma
prognosis
Translational Therapeutics
Tyrosine kinase
Proto-oncogene tyrosine-protein kinase Src
medicine.drug
Src
Signal Transduction
Subjects
Details
- ISSN :
- 00070920
- Database :
- OpenAIRE
- Journal :
- BRITISH JOURNAL OF CANCER, r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau, instname, British Journal of Cancer
- Accession number :
- edsair.doi.dedup.....c0a242f82c172f6fcde0626985384982