Targets for Breast Cancer Studied in Animal Models
Early-stage triple-negative breast cancer (TNBC) primarily relies on surgery and chemotherapy, yet its response is often suboptimal compared to other breast cancer subtypes. The development of targeted therapies is crucial to improve prognosis, enhance treatment efficacy and mitigate drug resistance. Identifying novel therapeutic pathways holds the potential to transform TNBC treatment.
- Categories
- Target Selection
Overview
Early-stage triple-negative breast cancer (TNBC) primarily relies on surgery and chemotherapy, yet its response is often suboptimal compared to other breast cancer subtypes. The development of targeted therapies is crucial to improve prognosis, enhance treatment efficacy and mitigate drug resistance. Identifying novel therapeutic pathways holds the potential to transform TNBC treatment. Here, we used Causaly to identify targets for TNBC studied in animal models.
TNBC: An Aggressive Breast Cancer
Breast cancer stands as one of the most prevalent of all cancers in the U.S., with more than 300,000 cases expected in 2023.¹ Predominantly affecting women, approximately 13% of women will be diagnosed with invasive breast cancer, and around 3% will die from this disease.²
Among the subtypes of breast cancer, triple-negative breast cancer (TNBC) emerges as one of the most aggressive, resulting in poor survival rates. Accounting for 10-15% of all breast cancers,³ TNBC lacks HER2 and estrogen/progesterone receptors, rendering traditional hormone therapies ineffective and thus, limits treatment options.
Treatment is challenging due to tumor heterogeneity, side effects, metastasis potential and chemo-resistance.⁴ Targeted therapies have the potential to revolutionize the TNBC landscape. Here, we used Causaly to identify potential targets of TNBC which have been studied in animal models.
Target Identification and Prioritization
Using Causaly, around 1,200 targets for TNBC were identified (Figure 1), around 950 of which are ranked in the top 25% of the most reputable journals. Since 2018, approximately 450 targets have been reported in primary data. Only around 100 of these targets have been studied in animal models, the majority of which have been studied in mice.
- Mouse: The knockdown of SHOC2, a scaffold protein which regulates Ras-effector signaling, was shown to significantly increase the sensitivity of TNBC cells to mTOR pathway inhibitor everolimus.⁵ Similarly, the suppression of SHOC2 in a xenograft mouse model enhanced tumor sensitivity to everolimus.⁵ These findings suggest that SHOC2 could mediate drug resistance of TNBCs to this drug, and therefore, may a promising therapeutic target.
- Rat: A study utilizing rat breast cancer model to assess the mechanism by which necrosis leads to poor clinical outcomes and metastasis showed that angiopoietin like-7 (Angptl7) regulates this process.⁶ Findings also implicated an association between Angptl7 and TNBCs with large necrotic zones, suggesting its potential a target for this breast cancer subtype.⁶
Conclusion
With Causaly, potential therapeutic targets for TNBC were rapidly extracted from biomedical literature. Here, SHOC2 and Angptl7, identified from murine and rat models respectively, present as prospective targets. These insights underscore the potential for advancing targeted therapeutic strategies, aiming for improved clinical outcomes in TNBC management.
References
- Siegel, R. L., Miller, K. D., Wagle, N. S., et. al., CA Cancer J. Clin., 2023;73(1):17-48. Source
- Giaquinto, A. N., Sung, H., Miller, K.D., et. al., CA Cancer J. Clin., 2022;72(1):524-541. Source
- Zagami, P., Carey, L. A., NPJ Breast Cancer, 2022;8(1):95. Source
- Shokooh, M. K., Emami, F., Jeong, J. H., et. al., Pharmaceutics., 2021;13(2):287. Source
- Geng, W., Cao, M., Dong, K., et. al., Cancer Biol. Ther., 2023;24(1):2206362. Source
- Yamamoto, A., Huang, Y., et. al., Proc. Natl. Acad. Sci. U.S.A., 2023;120(10):e2214888120. Source
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