RAS as Supporting Actor in Breast Cancer
1Department of Neuroscience, Biomedicine and Movement, University of Verona, Verona, Italy.
Abstract:
Oncogenic activation of RAS isoforms leads tumor initiation and progression in many types of cancers and is gaining increasing interest as target for novel therapeutic strategies. In sharp contrast with other types of cancer, the importance of RAS in breast tumorigenesis has long been undermined by the low frequency of its oncogenic mutation in human breast lesions. Nevertheless, a wealth of studies over the last years have revealed how the engagement of RAS function might be mandatory downstream varied oncogenic alterations for the progression, metastatic dissemination, and therapy resistance in breast cancers. We review herein the major studies over the last three decades which have explored the controversial role of RAS proteins and their mutation status in breast tumorigenesis and have contributed to reveal their role as supporting actors, instead of as primary cause, in breast cancer.
Insights
RAS proteins are crucial for breast cancer progression, metastasis, and therapy resistance, despite rare mutations. These findings highlight RAS as a key therapeutic target in breast cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genetics
Background:
- RAS proteins are critical oncogenic drivers in numerous cancers, but their role in breast cancer has been historically underestimated due to low mutation frequencies.
- Recent research indicates RAS pathway engagement is essential for breast cancer progression, metastasis, and therapeutic resistance, irrespective of direct mutation.
- This underscores a complex, indirect role for RAS in breast tumorigenesis.
Purpose of the Study:
- To review the literature on the role of RAS proteins in breast cancer over the past three decades.
- To explore the controversial involvement and mutation status of RAS in breast tumorigenesis.
- To elucidate the function of RAS as a supporting factor rather than a primary driver in breast cancer.
Main Methods:
- Comprehensive literature review of studies spanning 30 years.
- Analysis of research investigating RAS protein function and mutation status in breast cancer.
- Synthesis of findings on RAS involvement in tumor initiation, progression, metastasis, and therapy resistance.
Main Results:
- RAS oncogenic mutations are infrequent in human breast lesions, contrasting with other cancers.
- RAS pathway activation is indispensable for breast cancer progression, metastatic spread, and resistance to therapies.
- RAS proteins function as critical facilitators ('supporting actors') in breast cancer development, downstream of other oncogenic alterations.
Conclusions:
- The role of RAS in breast cancer is complex, acting as a key mediator of tumor progression and resistance.
- Targeting the RAS pathway presents a promising therapeutic strategy for breast cancer, even in the absence of direct RAS mutations.
- Future research should focus on understanding how RAS is engaged downstream of various oncogenic events in breast cancer.
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