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Molecular Mechanisms and Emerging Therapeutic Targets of Triple-Negative Breast Cancer Metastasis.

ABSTRACT: Breast cancer represents a highly heterogeneous disease comprised by several subtypes with distinct histological features, underlying molecular etiology and clinical behaviors. It is widely accepted that triple-negative breast cancer (TNBC) is one of the most aggressive subtypes, often associated with poor patient outcome due to the development of metastases in secondary organs, such as the lungs, brain, and bone. The molecular complexity of the metastatic process in combination with the lack of effective targeted therapies for TNBC metastasis have fostered significant research efforts during the past few years to identify molecular "drivers" of this lethal cascade. In this review, the most current and important findings on TNBC metastasis, as well as its closely associated basal-like subtype, including metastasis-promoting or suppressor genes and aberrantly regulated signaling pathways at specific stages of the metastatic cascade are being discussed. Finally, the most promising therapeutic approaches and novel strategies emerging from these molecular targets that could potentially be clinically applied in the near future are being highlighted.

SUBMITTER: Neophytou C

PROVIDER: S-EPMC5827095 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Molecular Mechanisms and Emerging Therapeutic Targets of Triple-Negative Breast Cancer Metastasis.

Neophytou Christiana C Boutsikos Panagiotis P Papageorgis Panagiotis P

Frontiers in oncology 20180222

Breast cancer represents a highly heterogeneous disease comprised by several subtypes with distinct histological features, underlying molecular etiology and clinical behaviors. It is widely accepted that triple-negative breast cancer (TNBC) is one of the most aggressive subtypes, often associated with poor patient outcome due to the development of metastases in secondary organs, such as the lungs, brain, and bone. The molecular complexity of the metastatic process in combination with the lack of ...[more]

PMID: 29520340

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Project description:Personalised approaches to the management of all solid tumours are increasing rapidly, along with wider accessibility for clinicians. Advances in tumour characterisation and targeted therapies have placed triple-negative breast cancers (TNBC) at the forefront of this approach. TNBC is a highly heterogeneous disease with various histopathological features and is driven by distinct molecular alterations. The ability to tailor individualised and effective treatments for each patient is of particular importance in this group due to the high risk of distant recurrence and death. The mainstay of treatment across all subtypes of TNBC has historically been cytotoxic chemotherapy, which is often associated with off-target tissue toxicity and drug resistance. Neoadjuvant chemotherapy is commonly used as it allows close monitoring of early treatment response and provides valuable prognostic information. Patients who achieve a complete pathological response after neoadjuvant chemotherapy are known to have significantly improved long-term outcomes. Conversely, poor responders face a higher risk of relapse and death. The identification of those subgroups that are more likely to benefit from breakthroughs in the personalised approach is a challenge of the current era where several targeted therapies are available. This review presents an overview of contemporary practice, and promising future trends in the management of early TNBC. Platinum chemotherapy, DNA damage response (DDR) inhibitors, immune checkpoint inhibitors, inhibitors of the PI3K-AKT-mTOR, and androgen receptor (AR) pathways are some of the increasingly studied therapies which will be reviewed. We will also discuss the growing evidence for less-developed agents and predictive biomarkers that are likely to contribute to the forthcoming advances in this field. Finally, we will propose a framework for the personalised management of TNBC based upon the integration of clinico-pathological and molecular features to ensure that long-term outcomes are optimised.

Dataset Information

Molecular Mechanisms and Emerging Therapeutic Targets of Triple-Negative Breast Cancer Metastasis.

Publications

Molecular Mechanisms and Emerging Therapeutic Targets of Triple-Negative Breast Cancer Metastasis.

Similar Datasets

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