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Published on: June 12, 2021
Microenvironment, oncoantigens, and antitumor vaccination: lessons learned from BALB-neuT mice
Laura Conti1, Roberto Ruiu1, Giuseppina Barutello1
1Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino, Via Nizza 52, 10126 Torino, Italy.
Abstract:
The tyrosine kinase human epidermal growth factor receptor 2 (HER2) gene is amplified in approximately 20% of human breast cancers and is associated with an aggressive clinical course and the early development of metastasis. Its crucial role in tumor growth and progression makes HER2 a prototypic oncoantigen, the targeting of which may be critical for the development of effective anticancer therapies. The setup of anti-HER2 targeting strategies has revolutionized the clinical outcome of HER2(+) breast cancer. However, their initial success has been overshadowed by the onset of pharmacological resistance that renders them ineffective. Since the tumor microenvironment (TME) plays a crucial role in drug resistance, the design of more effective anticancer therapies should depend on the targeting of both cancer cells and their TME as a whole. In this review, starting from the successful know-how obtained with a HER2(+) mouse model of mammary carcinogenesis, the BALB-neuT mice, we discuss the role of TME in mammary tumor development. Indeed, a deeper knowledge of antigens critical for cancer outbreak and progression and of the mechanisms that regulate the interplay between cancer and stromal cell populations could advise promising ways for the development of the best anticancer strategy.
Insights
Targeting human epidermal growth factor receptor 2 (HER2) has improved breast cancer treatment, but resistance emerges. New strategies must target both cancer cells and the tumor microenvironment (TME) for better outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Human epidermal growth factor receptor 2 (HER2) gene amplification in ~20% of breast cancers drives aggressive disease and metastasis.
- Targeting HER2 has improved outcomes for HER2-positive breast cancer but is often limited by acquired drug resistance.
- The tumor microenvironment (TME) is increasingly recognized as a critical factor in the development of therapeutic resistance.
Purpose of the Study:
- To review the role of the TME in mammary tumor development and HER2-targeted therapy resistance.
- To explore how understanding cancer-TME interactions can inform novel anticancer strategies.
- To highlight the potential of targeting both cancer cells and the TME for improved therapeutic efficacy.
Main Methods:
- Review of existing literature on HER2-positive breast cancer, anti-HER2 therapies, and TME.
- Utilized insights from the BALB-neuT mouse model of HER2-positive mammary carcinogenesis.
- Analysis of antigen roles and cancer-stromal cell interplay mechanisms.
Main Results:
- HER2 is a key oncoantigen, and its targeting has revolutionized HER2-positive breast cancer treatment.
- Pharmacological resistance to anti-HER2 therapies is a significant clinical challenge.
- The TME significantly influences the efficacy of cancer therapies and the development of resistance.
Conclusions:
- Effective anticancer strategies must consider the TME alongside cancer cells to overcome resistance.
- Further research into TME components and cancer-stromal interactions is crucial for developing next-generation therapies.
- Targeting both cancer and its microenvironment offers a promising avenue for improved breast cancer treatment.
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