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Updated: Feb 28, 2026

Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
Emerging Protein Targets in Triple-Negative Breast Cancer: Beyond Conventional Therapy
Andrea Previtali1, Isabella Guardamagna2, Silvia Calandra1
1Department of Molecular Medicine, University of Pavia, 27100 Pavia, Italy.
Abstract:
Triple-negative breast cancer (TNBC) remains one of the most aggressive and therapeutically challenging breast cancer subtypes, lacking expression of estrogen receptor, progesterone receptor, and HER2. Conventional chemotherapy and immune checkpoint inhibitors provide some benefit, but resistance and relapse are frequent. The search for novel targets has therefore become central to developing more effective and durable therapies. Recent advances in proteomics, structural biology, and targeted protein degradation are rapidly expanding the repertoire of actionable molecules in TNBC. This review summarizes current and emerging therapeutic strategies for TNBC, with a focus on targeted approaches designed to address tumor heterogeneity and resistance mechanisms. To this end, recent advances in targeted therapies are examined, including immune checkpoint inhibitors, PARP inhibitors, Trop-2-directed antibody-drug conjugates, anti-angiogenic agents, PI3K/Akt/mTOR pathway inhibitors, androgen receptor antagonists, and CDK4/6 inhibitors, highlighting results from completed and ongoing clinical trials. In addition, we explore novel targets identified through integrative omics approaches, as well as the role of the tumor metabolism and microenvironment in modulating therapeutic efficacy. Finally, we outline innovative radiotherapy strategies based on targeted radiation delivery and biological integration with systemic therapies. Collectively, this review provides an updated and novel overview of the evolving TNBC therapeutic landscape and highlights promising directions for the development of next-generation, biomarker-driven treatment strategies aimed at improving patient outcomes, maintaining a broad perspective on a very large class of targets.
Insights
Triple-negative breast cancer (TNBC) is aggressive, but new targeted therapies show promise. This review covers emerging treatments like antibody-drug conjugates and pathway inhibitors to overcome resistance and improve outcomes for TNBC patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Triple-negative breast cancer (TNBC) is an aggressive subtype lacking ER, PR, and HER2 expression, presenting significant therapeutic challenges.
- Conventional treatments like chemotherapy and immunotherapy face frequent resistance and relapse, necessitating novel therapeutic strategies.
- Advances in proteomics, structural biology, and targeted protein degradation are identifying new targets for TNBC.
Purpose of the Study:
- To review current and emerging therapeutic strategies for TNBC.
- To focus on targeted approaches addressing tumor heterogeneity and resistance mechanisms.
- To provide an updated overview of the evolving TNBC therapeutic landscape.
Main Methods:
- Summarizing recent advances in targeted therapies including immune checkpoint inhibitors, PARP inhibitors, antibody-drug conjugates, and pathway inhibitors.
- Examining clinical trial results for various targeted agents.
- Exploring novel targets identified through omics approaches and the role of tumor metabolism and microenvironment.
- Outlining innovative radiotherapy strategies.
Main Results:
- Targeted therapies, including immune checkpoint inhibitors, PARP inhibitors, Trop-2-directed antibody-drug conjugates, and pathway inhibitors, show potential in clinical trials.
- Integrative omics approaches are identifying novel therapeutic targets.
- Tumor metabolism and microenvironment significantly influence therapeutic efficacy.
- Innovative radiotherapy strategies are being developed.
Conclusions:
- The TNBC therapeutic landscape is rapidly evolving with promising targeted approaches.
- Biomarker-driven strategies are crucial for developing next-generation treatments.
- Addressing tumor heterogeneity and resistance mechanisms is key to improving patient outcomes.
- Further research into novel targets, metabolism, microenvironment, and radiotherapy integration is warranted.
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