FoxM1 mediates resistance to herceptin and paclitaxel.

Cancer Res

Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, College of Medicine, Chicago, Illinois 60607-7170, USA.

Published: June 2010

Inherent and acquired therapeutic resistance in breast cancer remains a major clinical challenge. In human breast cancer samples, overexpression of the oncogenic transcription factor FoxM1 has been suggested to be a marker of poor prognosis. In this study, we report that FoxM1 overexpression confers resistance to the human epidermal growth factor receptor 2 monoclonal antibody Herceptin and microtubule-stabilizing drug paclitaxel, both as single agents and in combination. FoxM1 altered microtubule dynamics to protect tumor cells from paclitaxel-induced apoptosis. Mechanistic investigations revealed that the tubulin-destabilizing protein Stathmin, whose expression also confers resistance to paclitaxel, is a direct transcriptional target of FoxM1. Significantly, attenuating FoxM1 expression by small interfering RNA or an alternate reading frame (ARF)-derived peptide inhibitor increased therapeutic sensitivity. Our findings indicate that targeting FoxM1 could relieve therapeutic resistance in breast cancer.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2893542PMC
http://dx.doi.org/10.1158/0008-5472.CAN-10-0545DOI Listing

Publication Analysis

Top Keywords

breast cancer
12
therapeutic resistance
8
resistance breast
8
confers resistance
8
foxm1
7
resistance
5
foxm1 mediates
4
mediates resistance
4
resistance herceptin
4
herceptin paclitaxel
4

Similar Publications

Air pollution and breast cancer risk: a Mendelian randomization study.

Int J Environ Health Res

January 2025

Department of Oncology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.

Previous research yields inconsistent findings on the association between air pollution and breast cancer risk, with no definitive causal relationship established. To address this, we conducted a two-sample Mendelian randomization study on data from the IEU open GWAS databases and the Breast Cancer Association Consortium to explore the potential link between air pollution (including PM, PM absorbance, PM, PM, NO, and NO) and breast cancer risk. We found that PM (odds ratio (OR) = 1.

View Article and Find Full Text PDF

Apatinib and trastuzumab-based chemotherapy for heavily treated primary trastuzumab-resistant metastatic breast cancer.

J Cancer Res Ther

December 2024

Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital and Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, People's Republic of China.

Background: The low incidence and poor prognosis primary trastuzumab resistance (PTR) in HER2-positive breast cancer has limited research into possible treatments. Thus, it remains unclear whether this group of patients could benefit from nontargeting HER2 antiangiogenic therapy.

Patients And Methods: We collected the medical data for HER2-positive patients with PTR who received apatinib 250 mg and trastuzumab-based chemotherapy (ATBC) between March 18, 2017, and March 31, 2022.

View Article and Find Full Text PDF

Tumor-infiltrating lymphocytes (TILs) are key components of the tumor microenvironment (TME) and serve as prognostic markers for breast cancer. Patients with high TIL infiltration generally experience better clinical outcomes and extended survival compared to those with low TIL infiltration. However, as the TME is highly complex and TIL subtypes perform distinct biological functions, TILs may only provide an approximate indication of tumor immune status, potentially leading to biased prognostic results.

View Article and Find Full Text PDF

Reconfiguring Priorities: Breastfeeding Decision-making Among Young Breast Cancer Survivors.

Cancer Nurs

January 2025

Author Affiliations: Department Research, Hospital Germans Trias i Pujol, Universitat Autonòma de Barcelona; and NURECARE Research Group, Institut d'Investigació i Hospital Germans Trias i Pujol (IGTP), Ctra de Can Ruti, Camí de les Escoles (Dr Huertas-Zurriaga); Department Research, Institut Català Oncologia-Hospital Germans Trias i Pujol; Universitat Autonòma de Barcelona; GRIN Group, IDIBELL, Institute of Biomedical Research; and NURECARE Research Group, IGTP, Ctra de Can Ruti, Camí de les Escoles (Dr Cabrera-Jaime); Tecnocampus University and NURECARE Research Group, IGTP, Ctra de Can Ruti, Camí de les Escoles (Dr Navarri); Oncology Department, Hereditarian Cancer Program, Institut Català Oncologia-Hospital Germans Trias i Pujol, B-ARGO (Badalona Applied Research Group in Oncology), IGTP (Health Research Institute Germans Trias i Pujol), Universitat Autònoma de Barcelona (Dr Teruel-Garcia); and Nursing Research Group in Vulnerability and Health (GRIVIS); and Nursing Department, Faculty of Medicine, Universitat Autònoma de Barcelona (Dr Leyva-Moral), Badalona, Spain.

Background: Breast cancer survivors face unique challenges in breastfeeding decisions. Limited research exists on the experiences and decision-making processes of young women with breast cancer regarding breastfeeding.

Objective: To explain the decision-making processes of young women with breast cancer in relation to breastfeeding throughout the cancer trajectory.

View Article and Find Full Text PDF

Purpose: Mammary carcinoma is comprised heterogeneous groups of cells with different metastatic potential. 4T1 mammary carcinoma cells metastasized to heart (4THM), liver (4TLM) and brain (4TBM) and demonstrate cancer-stem cell phenotype. Using these cancer cells we found thatTGF-β is the top upstream regulator of metastatic process.

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!