MECHANISMS OF ENDOCRINE RESISTANCE IN BREAST CANCER

By C. Osborne, R. Schiff. Annual Review of Medicine, 2011

1,176 citations recorded by the source corpus.

The estrogen receptor (ER) pathway plays a pivotal role in breast cancer development and progression. Endocrine therapy to block the ER pathway is highly effective, but its usefulness is limited by common intrinsic and acquired resistance. Multiple mechanisms responsible for endocrine resistance have been proposed and include deregulation of various components of the ER pathway itself, alterations in cell cycle and cell survival signaling molecules, and the activation of escape pathways that can provide tumors with alternative proliferative and survival stimuli. Among these, increased expression or signaling of growth factor receptor pathways, especially the EGFR/HER2 pathway, has been associated with both experimental and clinical endocrine therapy resistance. New treatment combinations targeting ER and growth factor receptor signaling which block the crosstalk between these pathways and eliminate escape routes have been proven highly effective in preclinical models. Results of recent clinical studies, while partly supporting this approach, also highlight the need to better identify a priori the appropriate patients whose tumors are most likely to benefit from these specific co-targeting strategies.

Subfields: Cancer Research, Genetics, Oncology

View Paper: https://www.semanticscholar.org/paper/eb1b6d8a44963fd5e82648af5206a2cdcf75fe3d

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

1. Carlos L. Arteaga

In Genetics

1. Carlos L. Arteaga
2. Myles A. Brown
3. Roman Yelensky

In Oncology

1. Carlos L. Arteaga
2. Vincent A. Miller

Citations in the corpus

• Strategies for subtypes—dealing with the diversity of breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011 (2011, background): “Overcoming resistance to endocrine therapies An improved understanding of the mechanisms of endocrine therapy resistance includes the role of growth factors, integrins, stress kinases, and molecular pathways including PI3K/AKT and MEK/MAPK [41].”
• Emergence of constitutively active estrogen receptor-α mutations in pretreated advanced estrogen receptor positive breast cancer (2014, background): “Proposed mechanisms of resistance include activation of growth factor receptor, cell survival and cell-cycle signaling pathways, as well as stressinduced pathways (4, 5).”
• Single-cell RNA-seq enables comprehensive tumour and immune cell profiling in primary breast cancer (2017, neutral): “Rewired signalling pathway activation through other growth factor receptors, as well as a change in the subtype from that of the primary tumour in metastatic lesions 7 , may also arise from gene expression level heterogeneity in individual tumour cells.”