Purpose: Erlotinib (Tarceva, OSI-774) is a potent and specific inhibitor of the HER1/epidermal growth factor receptor (EGFR) tyrosine kinase. In phase II clinical studies, oral erlotinib monotherapy has shown antitumor activity in patients with advanced non-small cell lung cancer, head and neck cancer, and ovarian cancer after the failure of standard chemotherapy. We hypothesized that some tumors treated with multiple cytotoxic therapies may become more dependent on the HER1/EGFR signaling pathways for survival.

Experimental Design: The growth-inhibitory effect of erlotinib was tested on 10 pairs of chemosensitive, parental, and chemoresistant tumor cell lines.

Results: Enhanced sensitivity to erlotinib was observed in the doxorubicin-resistant human breast cancer cell line MCF-7, paclitaxel-resistant human ovarian carcinoma cell line A2780, and cisplatin-resistant human cervical carcinoma cell line ME180. The IC(50) values of erlotinib in the resistant cell lines were 2- to 20-fold lower than those in the corresponding parental cell lines. This enhanced sensitivity to erlotinib correlated with higher HER1/EGFR and phospho-HER1/EGFR expression when compared with the corresponding parental cell lines. Acquired resistance to cytotoxic agents was not associated with cross-resistance to erlotinib. AE-ME180/CDDP-resistant xenografts showed greater sensitivity to erlotinib than parental ME180 xenografts did.

Conclusions: Our findings suggest that acquired resistance to cytotoxic therapy in some tumors is associated with enhanced sensitivity to HER1/EGFR inhibitors, which correlates with increased HER1/EGFR expression. These data may explain some of the observed clinical activity of HER1/EGFR inhibitors in patients previously treated with multiple therapies. HER1/EGFR tyrosine kinase inhibitors may be more effective as second- or third-line treatment for certain patients with tumors that were previously treated with multiple chemotherapy regimens.

Download full-text PDF

Source
http://dx.doi.org/10.1158/1078-0432.CCR-04-0993DOI Listing

Publication Analysis

Top Keywords

enhanced sensitivity
16
cell lines
16
tyrosine kinase
12
treated multiple
12
sensitivity erlotinib
12
erlotinib
9
cell
9
her1/epidermal growth
8
growth factor
8
factor receptor
8

Similar Publications

Mosses and lichens are often used to assess atmospheric deposition of Pb. The most widely used method for determining this isotope is gamma spectrometric analysis. There is often a need to enhance the sensitivity of the method, which can be achieved by pre-concentrating Pb.

View Article and Find Full Text PDF

Construction of single probes for simultaneous detection of common trivalent metal ions has attracted much attention due to higher efficiency in analysis and cost. A naphthalimide-based fluorescent probe K1 was synthesized for selective detection of Al, Cr and Fe ions. Fluorescence emission intensity at 534 nm of probe K1 in DMSO/HO (9:1, v/v) was significantly enhanced upon addition of Al, Cr and Fe ions while addition of other metal ions (Li, Na, K, Ag, Cu, Fe, Zn, Co, Ni, Mn, Sr, Hg, Ca, Mg, Ce, Bi and Au) did not bring about substantial change in fluorescence emission.

View Article and Find Full Text PDF

Unraveling the potential mechanism and prognostic value of pentose phosphate pathway in hepatocellular carcinoma: a comprehensive analysis integrating bulk transcriptomics and single-cell sequencing data.

Funct Integr Genomics

January 2025

Institute of Infectious Diseases, Guangdong Province, Guangzhou Eighth People's Hospital, Guangzhou Medical University, 8 Huaying Road, Baiyun District, Guangzhou, 510440, China.

Hepatocellular carcinoma (HCC) remains a malignant and life-threatening tumor with an extremely poor prognosis, posing a significant global health challenge. Despite the continuous emergence of novel therapeutic agents, patients exhibit substantial heterogeneity in their responses to anti-tumor drugs and overall prognosis. The pentose phosphate pathway (PPP) is highly activated in various tumor cells and plays a pivotal role in tumor metabolic reprogramming.

View Article and Find Full Text PDF

Purpose: This case report aims to present a rare case of endometrial carcinosarcoma, a highly malignant tumor with a poor prognosis. The primary objective is to describe this unique case's clinical presentation, multimodal magnetic resonance imaging (MRI) features, typical histopathological characteristics and surgical treatment.

Methods: A detailed analysis of the patient's medical history, preoperative imaging evaluation, and treatment approach was conducted.

View Article and Find Full Text PDF

EOSnet: Embedded Overlap Structures for Graph Neural Networks in Predicting Material Properties.

J Phys Chem Lett

January 2025

Department of Physics, Rutgers University, Newark, New Jersey 07102, United States of America.

Graph Neural Networks (GNNs) have emerged as powerful tools for predicting material properties, yet they often struggle to capture many-body interactions and require extensive manual feature engineering. Here, we present EOSnet (Embedded Overlap Structures for Graph Neural Networks), a novel approach that addresses these limitations by incorporating Gaussian Overlap Matrix (GOM) fingerprints as node features within the GNN architecture. Unlike models that rely on explicit angular terms or human-engineered features, EOSnet efficiently encodes many-body interactions through orbital overlap matrices, providing a rotationally invariant and transferable representation of atomic environments.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!