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Published on: May 17, 2019
Data-Driven identification of chemopreventive agents for breast cancer
Deniz Can Güven1, Cemal Orhan2, Kazim Şahin2
1Department of Medical Oncology, Faculty of Medicine, University of Hacettepe, Ankara, Turkey
Abstract:
Preclinical animal models of breast cancer provide the opportunity to identify chemopreventive drugs with single-agent activity as well as effective multi-modality regimens for primary as well as secondary prevention in high-risk persons. Our group has used the 7,12-dimethylbenz(a)anthracene (DMBA) mouse model of carcinogen-induced breast cancer to explore the clinical potential of two tyrosine kinase inhibitors and a nucleoside analog as chemopreventive agents. All three agents exhibited promising preclinical activity both as monotherapy and as components of combination therapy with the standard chemotherapy drug paclitaxel. The tumors developing despite chemoprevention were not only small and grew slowly, but they also displayed a uniquely more pro-apoptotic protein expression profile. Hence, our experimental chemopreventive drugs were capable of preventing the development of aggressive mammary gland tumors with an apoptosis-resistant protein expression profile.
Insights
Preclinical breast cancer models identified promising chemopreventive drugs. These agents, including tyrosine kinase inhibitors and a nucleoside analog, reduced aggressive tumor development and promoted apoptosis.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Preclinical animal models are crucial for identifying effective breast cancer chemoprevention strategies.
- High-risk individuals benefit from primary and secondary prevention methods.
- The 7,12-dimethylbenz(a)anthracene (DMBA) mouse model simulates carcinogen-induced breast cancer.
Purpose of the Study:
- To evaluate the chemopreventive potential of specific tyrosine kinase inhibitors and a nucleoside analog.
- To assess the efficacy of these agents as monotherapy and in combination with paclitaxel.
- To analyze the characteristics of tumors that develop despite chemoprevention.
Main Methods:
- Utilized the DMBA-induced mouse model of breast cancer.
- Administered two tyrosine kinase inhibitors and one nucleoside analog.
- Tested agents as single agents and in combination with paclitaxel.
- Analyzed protein expression profiles, focusing on apoptosis markers.
Main Results:
- All three tested agents demonstrated promising preclinical chemopreventive activity.
- Both monotherapy and combination regimens showed efficacy.
- Tumors developing under chemoprevention were smaller, grew slower, and exhibited a pro-apoptotic profile.
- The experimental drugs prevented aggressive, apoptosis-resistant mammary tumors.
Conclusions:
- The evaluated tyrosine kinase inhibitors and nucleoside analog show significant potential for breast cancer chemoprevention.
- These agents can prevent the development of aggressive mammary tumors by altering the apoptotic profile.
- Further clinical investigation of these agents is warranted for high-risk populations.
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