Track topics on Twitter Track topics that are important to you
The human epidermal growth factor receptor 2 (HER2)-positive breast cancer with overexpression of HER2 accounts for approximately 25% of breast cancers and is more aggressive than other types of breast cancer. Lapatinib has been widely used as a HER2-targeted therapy, however, a number of patients develop lapatinib resistance and still suffer from poor prognosis. Therefore, it is essential to identify novel therapeutic targets that could overcome lapatinib resistance. In this study, we carried out phosphoproteomic analysis of lapatinib sensitive and resistant cell lines (SKBR3 and SKBR3-LR) using stable isotope labeling with amino acids in cell culture (SILAC). We identified 3808 phosphopeptides from 1807 proteins and then analyzed signaling pathways, Gene Ontology, and protein-protein interaction networks. Finally, we identified PAK2 as a therapeutic target from the network analysis and validated that PAK2 knockdown and PAK inhibitor treatment resensitize the lapatinib resistant cells to lapatinib. This results suggest that PAK2 is a potent therapeutic target to overcome acquired lapatinib resistance in HER2-positive breast cancer cells.
This article was published in the following journal.
Name: Biochemical and biophysical research communications
Cisplatin-based chemotherapy is currently part of the standard of care for bladder cancer (BC). Unfortunately, some patients respond poorly to chemotherapy and have acquired or developed resistance. T...
Most bioanalytical methods reported in literature for the quantitation of lapatinib in human plasma are either for lapatinib alone or lapatinib administered along with other tyrosine kinase inhibitors...
Synaptic cytoskeleton dysfunction represents a common pathogenesis in neurodevelopmental disorders, such as autism spectrum disorder (ASD). The serine/threonine kinase PAK2 is a critical regulator of ...
The epidermal growth factor receptor (1) is a major oncogene in triple negative breast cancer (TNBC), but the use of EGFR targeted tyrosine kinase inhibitors (TKI) and therapeutic monoclonal antibodie...
Hepatitis B virus-encoded X protein (HBx) plays a pivotal role in hepatocellular carcinoma (HCC) progression and treatment resistance. Interestingly, our previous study unexpectedly showed that full-l...
In this research study we are studying the effects of the combination of lapatinib plus Herceptin in subjects with breast cancer that has spread outside of the breast. We are also studying...
Study to evaluate the effect of lapatinib, a breast cancer resistance protein (BCRP) inhibitor, on the pharmacokinetics (PK) of JTZ-951 and to evaluate the safety and tolerability of JTZ-9...
The EGF19060 study is a rollover study to evaluate the long term safety of lapatinib and to provide lapatinib to patients who had a positive response in previous lapatinib studies until la...
RATIONALE: Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as vinorelbine, work in different ways to s...
RATIONALE: Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase I trial is studying the side effects and best dose of l...
An inherited autosomal recessive trait, characterized by peripheral resistance to THYROID HORMONES and the resulting elevation in serum levels of THYROXINE and TRIIODOTHYRONINE. This syndrome is caused by mutations of gene THRB encoding the THYROID HORMONE RECEPTORS BETA in target cells. HYPOTHYROIDISM in these patients is partly overcome by the increased thyroid hormone levels.
Works consisting of studies using a quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc. It is often an overview of clinical trials. It is usually called a meta-analysis by the author or sponsoring body and should be differentiated from reviews of literature.
A technique for analysis of the chemical composition of molecules. A substance is bombarded with monochromatic ELECTRONS. Some of the electrons passing through the specimen will lose energy when they ionize inner shell electrons of the atoms in the specimen. The energy loss is element dependent. Analysis of the energy loss spectrum reveals the elemental composition of a specimen. ENERGY-FILTERED TRANSMISSION ELECTRON MICROSCOPY is a type of electron energy loss spectroscopy carried out in electron microscopes specially outfitted to analyze the spectrum of electron energy loss.
A method of chemical analysis based on the detection of characteristic radionuclides following a nuclear bombardment. It is also known as radioactivity analysis. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
A type of strength-building exercise program that requires the body muscle to exert a force against some form of resistance, such as weight, stretch bands, water, or immovable objects. Resistance exercise is a combination of static and dynamic contractions involving shortening and lengthening of skeletal muscles.
Bladder Cancer Brain Cancer Breast Cancer Cancer Cervical Cancer Colorectal Head & Neck Cancers Hodgkin Lymphoma Leukemia Lung Cancer Melanoma Myeloma Ovarian Cancer Pancreatic Cancer ...