Stem Cell Targeting Natural Products for Therapy-Resistant Triple Negative Breast Cancer

Article Sidebar

PDF
Published Jun 29, 2025
DOI: https://doi.org/10.18103/mra.v13i6.6584

Downloads

Download data is not yet available.

Submit your own article

Register as an author to reserve your spot in the next issue of the Medical Research Archives.

Author Registration

Join the Society

The European Society of Medicine is more than a professional association. We are a community. Our members work in countries across the globe, yet are united by a common goal: to promote health and health equity, around the world.

Join Europe’s leading medical society and discover the many advantages of membership, including free article publication.

Membership

Main Article Content

Nitin T. Telang
Cancer Prevention Research Program, Palindrome Liaisons Consultants, Montvale, NJ 07645-1559, USA

Abstract

Background: The treatment options for breast cancer are dependent on the expression status of hormones and growth factor receptors. Hormone receptor positive Luminal A and Luminal B breast cancer subtypes exhibit favorable response to targeted endocrine therapy and/or human epidermal receptor-2 (HER-2) HER-2 therapy respectively. Hormone receptor negative, HER positive HER-2-enriched subtypes respond only to HER-2 targeted therapy. Hormone receptor negative and HER-2 negative triple negative (TNBC) subtypes respond only to conventional cytotoxic chemotherapy, and are notable for the presence of putative stem cell population. These subtype selective treatment options are universally associated with phenotypic therapy resistance, leading to emergence of chemo-resistant cancer initiating stem cell population that is responsible for initiation, progression and recurrence of therapy-resistant breast cancer. These limitations emphasize development of reliable drug-resistant cancer stem cell model for TNBC and identification of novel testable alternatives with stem cell selective efficacy.


Objectives: The present review article provides an overview of published evidence for i) Molecular characterization of TNBC subtype, ii) Limitations relevant to mainstream treatment options and advantages of natural products as testable therapeutic alternatives, and iii) Development and characterization of reliable drug-resistant TNBC stem cell model.


Conclusion: Published evidence discusses relevant information regarding molecular classification of TNBC subtype, significance of natural products as testable alternatives for TNBC subtype and applicability of drug-resistant stem cell model to investigate stem cell targeting efficacy of natural products.


Future Research: Collectively, discussed evidence defines a scientifically robust rationale to undertake future investigations on patient derived tumor explants and patient derived tumor organoids as a valuable strategy to reduce extrapolation of preclinical data for their clinical relevance and translatability for cancer stem cell targeting efficacy of natural products on breast cancer.

Keywords: Triple negative breast cancer, Therapy resistant stem cell, Natural products

Article Details

How to Cite
TELANG, Nitin T.. Stem Cell Targeting Natural Products for Therapy-Resistant Triple Negative Breast Cancer. Medical Research Archives, [S.l.], v. 13, n. 6, june 2025. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/6584>. Date accessed: 15 july 2025. doi: https://doi.org/10.18103/mra.v13i6.6584.
ABNT APA BibTeX CBE EndNote - EndNote format (Macintosh & Windows) MLA ProCite - RIS format (Macintosh & Windows) RefWorks Reference Manager - RIS format (Windows only) Turabian
Issue
Vol 13 No 6 (2025): Vol.13, Issue 6, June 2025
Section
Review Articles

The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.

 

References

1. American Cancer Society Fact and Figures 2025, American Cancer Society, Atlanta GA, USA. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-and-figures/2025/2025-cancer-facts-and-figures.pdf. Accessed on February 25, 2025.-
2. Gardishar WJ, Moran MS, Abrahan J: NCCN Clinical Practice Guidelines in Oncology: Breast Cancer Version 4, National Comprehensive Network: Plymouth Meeting, PA, USA, 2022. Available online: https://ww.nccn.org Accessed on 25, February 2025.
3. Lehmann BD, Colaprico A, Silva TC, et al: Multi-omics analysis identifies therapeutic vulnerabilities in triple negative breast cancer subtypes Nat. Commun. 2021, 12: 6276.
4. Neve RM, Chin K, Fridlyand J, et al: A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes. Cancer Cell 2006, 10: 515-527. Doi: 10.1016/j.ccr2006.10.008.
5. Shapira L, Lee A, Vora R, Budman DR: P53 mutations in triple negative breast cancer upregulate endosomal recycling of epidermal growth factor receptor (EGFR) increasing its oncogenic potency. Crit. Rev. Oncology/Hematology. 2013, 88: 284-292. Doi: 10.1016/j.critrevonc.2013.05.003.
6. Costa R, Shah AN, Santa-Maria CA, et al: Targeting epidermal growth factor receptor in triple negative breast cancer: New discoveries and practical insights for drug development. Cancer Treatment Review. 2017, 53: 111-119. Doi: 10.1016//j.ctrv.2016.12.010.
7. Ye L, Jia Y, Ji KE, et al: Traditional Chinese medicine in prevention and treatment of breast cancer and metastasis. Oncol. Letts. 2015, 10: 1240-1250. Doi: 10.3892/ol.2015.3459.
8. Hong M, Tan HY, Li S, et al: Cancer stem cells: The potential targets of Chinese medicines and their active compounds. Int. J. Mol. Sci. 2016, 17: 993.
9. Naujokat C, Mc Kee DL: The big five phytochemicals targeting the cancer stem cells: Curcumin, EGCG, Sulforaphane, resveratrol, and genistein. Cur. Med. Chem. 2021, 28: 4321-4342.2021. Doi: 10.2174/0929867327666200228110738.
10. Yang Z, Zhang Q, Yu L, et al: The signaling pathways and targets of traditional Chinese medicine and natural medicine in triple negative breast cancer. J. Ethno-pharmacol. 2021, 264: 113249. Doi: 10.1016/jep.2020.113249.
11. Zhu M, Liu Y, Wen Z, et al: Exploration of Chinese medicine comprehensive treatment of triple negative breast cancer based on molecular pathology mechanisms. Breast Cancer Targets Ther. 2025, 17: 289-304. Doi: 10.2147/BCTT.S511059..
12. Telang N: Natural phytochemicals as testable therapeutic alternatives for HER-2-enriched breast cancer. World Acad. Sci. J. 2020, 2: 19. Doi: 10.3892/wasj.2020.60
13. Telang NT, Nair HB, Wong GYC: Growth inhibitory efficacy of Chinese herbs in a cellular model for triple negative breast cancer. Pharmaceuticals (Basel) 2021, 14: 1318. Doi: 10.3390/ph14121318.
14. Telang N: Drug-resistant stem cell model for hormone responsive Luminal A breast cancer. Med. Res. Arch. 2023, 11: 3556. Doi: https://doi.org/10.18103/mrav11i2.3556.
15. Lytle NK, Barber NG, Reya T: Stem cell fate in cancer growth, progression and therapy resistance. Nat. Rev. Cancer 2018, 18: 669-680. Doi: 10.1038/s41568-018-0056-x.
16. Nunes T, Hamdan D, El Boutachtaoui MD, et al: Targeting cancer stem cells to overcome chemo-resistance. Int. J. Mol. Sci. 2018, 19: 4036.
17. Yager R, Solit DB: overcoming adaptive resistance to RAS inhibitors through vertical pathway targeting. Clin. Cancer Res. 2020, 26: 1538-1540. Doi: 10.1158/1078-0432.CCR-19-4060.
18. Takahashi K, Tanabe K, Ohnuki M, et al: Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007, 131: 861-872. Doi: 10.1016/jcell.2007.11.019.
19. Park IH, Zhao R, West JA, et al: Reprogramming of human somatic cells to pluripotency with defined factors. Nature 2008, 451: 141-146. Doi: 10.1038/nature06534
20. Telang N, Li G, Katdare M, et al: Inhibitory effects of Chinese nutritional herbs in isogenic breast carcinoma cells with modulated estrogen receptor function. Oncol. Letts. 2016, 12: 3949-3957. Doi: 10.3892/ol.2016.5197.
21. Telang N: Natural bioactive agents: Testable stem cell-targeting alternatives for therapy resistant breast cancer. Int. J. mol. Sci. 2025, 26: 2529.Doi: https://doi.org/10.3390/ijms26062529.
22. Berman TA, Ben-Ayre E, Kienle GS, et al: Integrating botanicals in to oncology care: Consideration of FDA regulation of botanical products and botanical clinical trials. Clin. Cancer Res. 2025, 31: 1556-1572. Doi: 10.1158/1078-0432.CCR-24-3419.
23. Jan A, Sofi S, Jan N, Mir MA: An update on cancer stem cell survival pathways involved in chemo-resistance in triple negative breast cancer. Future Oncol. 2025, 21: 715-735. Doi: 10.1080/14796694.2025.2461443
24. Manogaran P, Umapathy D, Karthikeyan M, et al: Dietary phytochemicals as a potential source for targeting cancer stem cells. Cancer Investig. 2021, 39: 349-368. Doi: 10.1080/07357907.2021.1894569.
25. Mengitsu BA, Tsegaw T, Demessie Y, et al: Comparative review of drug-resistance in mammalian cancer stem cells: Implications for cancer therapy. Cancer Cell Int. 2024, 24: 406. Doi: 10.1186/s12935-024-03558-0.
26. Elbaiomy MA, Tamer A, Atwan N, et al: Clinical impact of breast cancer stem cells in metastatic breast cancer patients. J. Oncol. 2020, 2561726. Doi: 10.1155/2020/2561726.eCollection2020.
27. Telang N: Stem cell targeted therapeutic approaches for molecular subtypes of clinical breast cancer. World Acad. Sci. J 2019, 1: 20-24. Doi: 10.3892/wasj.2018.3
28. Blanchard Z, Brown EA, Ghazaryan A, et al: PDX models for functional precision oncology and discovery science. Nat. Rev. Cancer 2025, 25: 153-166. Doi: 10.1038/s41568-024-00779-3.
29. Meng S, Cao Y, Lu LO, et al: Quercetin promotes the chemo-sensitivity in organoids derived from patients with breast cancer. Breast cancer Targets Ther. 2024, 16: 993-1004. Doi: 10.2147/BCTT.S494901.