Triple-Negative Breast Cancer: Heterogeneity, Tumor Microenvironment and Targeted Therapy

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Background

Triple-negative breast cancer (TNBC) is a complex and aggressive subtype of breast cancer that lacks significant levels of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression, which makes it a difficult to treat clinical entity. The management of TNBC imposes a heavy economic burden on the healthcare system and represents a major challenge for both clinicians and patients. Despite the tremendous advances in breast cancer treatment, the poor overall survival of TNBC patients - particularly those with metastatic or recurrent disease - has remained essentially unchanged over the past decades. This is largely due to the aggressive nature of the disease and the unavailability of defined molecular targets in TNBC. Other factors that contribute to the poor prognosis of TNBC include the extreme heterogeneity of the tumor at the molecular level as well as the histopathological level and the complex tumor microenvironment. Therefore, novel therapeutic options for different subtypes of TNBC, particularly those targeting strategies taking into account the heterogeneity and the tumor microenvironment, are urgently needed and have become an area of active investigation in TNBC research.

Although TNBC progression involves multiple genetic and epigenetic alterations, targetable ones are rare, which has hindered the development of successful targeted therapeutic strategies. Emerging therapeutic targets for TNBC include poly (ADP-ribose) polymerases, tyrosine kinases (receptor and non-receptor type), the androgen receptor, immune checkpoints, etc. However, most targeted agents tested so far, except for poly (ADP-ribose) polymerase inhibitors and immune checkpoint blockers, have demonstrated low overall activity in unselected TNBC.

This Research Topic is dedicated to publishing recent preclinical and clinical studies concerning novel targeted therapeutic options for TNBC. Those manuscripts that consider the highly heterogeneous nature of the disease and the complexity of the microenvironment are particularly welcome. It is hoped that promising therapeutic agents and/or methods will be identified through vigorous experimental investigation and validation with the ultimate goal of improving disease management and quality of life of TNBC patients.

We welcome submissions of Original Research, Review articles, and Mini-reviews, focusing on but not limited to, the following aspects:
1) Molecular Heterogeneity and Subtyping of TNBC: New Discoveries and Targeting Opportunities
2) Targeting Signaling Alterations and Epigenetic Modifications in TNBC
3) Cancer Stem Cells and Treatment Refraction in TNBC: Molecular Mechanisms and Novel Therapeutic Strategies
4) Angiogenesis, the Tumor Microenvironment, and Metabolic Reprogramming as Novel Therapeutic Targets in TNBC
5) Novel Immune-based Therapeutic Strategies for TNBC

Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.

Keywords: Molecular subtyping, Tumor microenvironment, Targeted Therapy, Triple-negative breast cancer, Cancer stem cells

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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