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Updated: May 9, 2025
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
Targeting Triple-Negative Breast Cancer: Resistance Mechanisms and Therapeutic Advancements
Rachana Raman1,2, Shristi Debata3, Thirupugal Govindarajan4
1Photoceutics and Regeneration Laboratory, Department of Biotechnology, Centre for Microfluidics, Biomarkers, Photoceutics and Sensors (μBioPS), Manipal Institute of Technology, Manipal Academy of Higher Education, Manipal, Karnataka, India.
Background:
Triple-negative breast cancer (TNBC) is one of the most heterogeneous and menacing forms of breast cancer, with no sustainable cure available in the current treatment landscape. Its lack of targets makes it highly unresponsive to various treatment modalities, which is why chemotherapy continues to be the primary form of treatment, despite the high rates of patients developing chemoresistance. In recent years, however, there has been significant progress in identifying and understanding the role of several aspects that might contribute to genomic instability and other hallmarks of cancer, including cellular proteins, immune targets, and epigenetic mechanisms, which are desirable as they permit reversibility easier than the often-adamant genetic changes.
Methods:
A literature review was conducted on the role of various TNBC associated biomarkers, their therapeutic applications, and their role in tumorigenesis and tumor maintenance, with a focus on linking both the driving biological mechanisms and emerging treatment options for TNBC.
Conclusions:
Shifting the focus of treatment to identify crucial tumor cell subpopulations and associated biomarkers, such as local immune cell populations and cancer stem cells, could potentially solve or simplify decades' worth of problems that are associated with TNBC, bolstering early detection and the evolution of precision medicine and treatment. The techniques that can be used here are epigenetic analysis and RNA sequencing. Biomarkers, such as PD-L1, survivin, and ABC transporters, are implicated in several crucial processes that maintain tumors, such as cell proliferation, metastasis, immunosuppression, and stemness. Complex treatment options such as, immunotherapy, pathway inhibition, PARP inhibition, virotherapy, and RNA targeting have been considered for TNBC. Phytochemicals are also being considered as a treatment modality for TNBC, as a supplement to chemotherapy and radiation therapy, or as sole treatment.
Insights
Triple-negative breast cancer (TNBC) is a challenging cancer due to its heterogeneity and chemoresistance. Targeting specific biomarkers and exploring novel therapies like immunotherapy and phytochemicals offers new hope for precision medicine.
Area of Science:
- Oncology
- Genomics
- Immunology
Background:
- Triple-negative breast cancer (TNBC) is a heterogeneous and aggressive cancer lacking targeted therapies.
- Chemotherapy remains the primary treatment, but chemoresistance is a significant challenge.
- Genomic instability, cellular proteins, immune targets, and epigenetic mechanisms are key areas of research.
Purpose of the Study:
- To review TNBC-associated biomarkers and their therapeutic potential.
- To link biological mechanisms driving TNBC with emerging treatment strategies.
- To explore novel approaches for TNBC management.
Main Methods:
- Literature review of TNBC biomarkers, therapeutic applications, and tumorigenesis.
- Focus on linking biological mechanisms with treatment options.
- Analysis of epigenetic modifications and RNA sequencing data.
Main Results:
- Biomarkers like PD-L1, survivin, and ABC transporters are crucial for tumor maintenance (proliferation, metastasis, immunosuppression, stemness).
- Emerging treatments include immunotherapy, pathway/PARP inhibition, virotherapy, and RNA targeting.
- Phytochemicals show promise as adjunct or sole treatments.
Conclusions:
- Focusing on tumor subpopulations and biomarkers (immune cells, cancer stem cells) can advance TNBC treatment.
- Epigenetic analysis and RNA sequencing are key techniques for biomarker discovery.
- Precision medicine approaches, including novel therapies and phytochemicals, are vital for improving TNBC outcomes.
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