The introduction of trastuzumab therapy markedly improved the poor prognosis associated with HER2-amplified breast cancers. Despite this, the presence of primary and acquired resistance to trastuzumab treatment remains a significant common challenge. The identification of resistance mechanisms and the incorporation of new drugs that achieve a better blockade of HER family receptors signaling have resulted in improved outcomes. The phosphatidylinositol 3'-kinase/protein kinase B/mammalian target of rapamycin pathway, cross-talk with estrogen receptors, immune response, cell cycle control mechanisms, and other tyrosine kinase receptors such as insulin-like growth factor I receptor are potential pathways involved in trastuzumab resistance. Different therapeutic interventions targeting these pathways are currently under evaluation.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4811269PMC
http://dx.doi.org/10.4137/CMO.S34537DOI Listing

Publication Analysis

Top Keywords

resistance trastuzumab
8
her2-amplified breast
8
mechanisms resistance
4
trastuzumab
4
trastuzumab her2-amplified
4
breast cancer
4
cancer strategies
4
strategies overcome
4
overcome introduction
4
introduction trastuzumab
4

Similar Publications

Human epidermal growth factor receptor 2 (HER2) is a critical biomarker and therapeutic target in gastric/gastroesophageal junction (G/GEJ) cancers, despite the initial success of HER2-targeted therapies, such as trastuzumab, resistance to these drugs has emerged as a major impediment to effective long-term treatment. This review examines the mechanisms of drug resistance in HER2-positive G/GEJ cancer, the primary mechanisms of resistance explored include alterations in the HER2 receptor itself, such as mutations and changes in expression levels, as well as downstream signaling pathways, and interactions with the tumor microenvironment (TME). Furthermore, the review discusses the Novel therapeutic approaches, including the use of antibody-drug conjugates (ADCs) and combination therapies are assessed for their potential to enhance outcomes.

View Article and Find Full Text PDF

Bioinformatics Analysis of Programmed Death-1-Trastuzumab Resistance Regulatory Networks in Breast Cancer Cells.

Asian Pac J Cancer Prev

January 2025

Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada Sekip Utara II, 55281 Yogyakarta, Indonesia.

Objective: Programmed cell death-1 (PD-1, encoded by PDCD1) regulatory network participates in glioblastoma multiforme development. However, such a network in trastuzumab-resistant human epidermal growth factor receptor 2-positive (HER2+) breast cancer remains to be determined. Accordingly, this study was aimed to explore the PD-1 regulatory network responsible for the resistance of breast cancer cells to trastuzumab through a bioinformatics approach.

View Article and Find Full Text PDF

Research into the role of probiotics-often referred to as "living supplements"-in cancer therapy is still in its early stages, and uncertainties regarding their effectiveness remain. Relevantly, chemopreventive and therapeutic effects of probiotics have been determined. There is also substantial evidence supporting their potential in cancer treatment such as immunotherapy.

View Article and Find Full Text PDF

Pre-Clinical Rationale for Amcenestrant Combinations in HER2+/ER+ Breast Cancer.

Int J Mol Sci

January 2025

Cancer Biotherapeutics Research Group, Life Sciences Institute, School of Biotechnology, Dublin City University, Dublin 9, D09 NR58 Dublin, Ireland.

HER2-positive/oestrogen receptor-positive (HER2+/ER+) represents a unique breast cancer subtype. The use of individual HER2- or ER-targeting agents can lead to the acquisition of therapeutic resistance due to compensatory receptor crosstalk. New drug combinations targeting HER2 and ER could improve outcomes for patients with HER2+/ER+ breast cancer.

View Article and Find Full Text PDF

Investigation of Heterogeneity to Overcome Trastuzumab Resistance in HER2-Positive Breast Cancer.

Biology (Basel)

December 2024

Department of Medical Biology, Faculty of Medicine, Recep Tayyip Erdogan University, 53100 Rize, Turkey.

HER2-positive breast cancer has an aggressive tumour progression among breast cancers characterized by the overexpression of HER2. Trastuzumab is an FDA-approved drug and has significantly improved outcomes for patients; however, drug resistance remains a major challenge. Tumour heterogeneity, describing genetic, epigenetic, and phenotypic differences within and between tumours, complicates tumour treatment and contributes to drug resistance.

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!