EC Pharmacology And Toxicology

Review Article Volume 13 Issue 3 - 2025

Stem Cell Therapy in Progression of Breast Cancer-An Overview

M Suchitra1*, Pratibha GS2, CL Sindhura3, Binoy Varghese Cheriyan4 and Priyanka Gondhale5

1Department of Pharmaceutical Analysis, Narayana Pharmacy College, Nellore, Andhra Pradesh, India
2Department of Pharmacognosy, Bapuji Pharmacy College, Davanagere, Karnataka, India
3Department of Pharmacy Practice, Narayana Pharmacy College, Nellore, Andhra Pradesh, India
4Department of Pharmaceutical Chemistry, Saveetha College of Pharmacy, Saveetha Institute of Medical and Technical Science, Saveetha University, Tamilnadu, India
5Department of Pharmaceutical Chemistry, School of Pharmacy, Vishwakarma University, VU Pune, Maharashtra, India
*Corresponding Author: M Suchitra, HOD and Professor, Department of Pharmaceutical Analysis, Narayana Pharmacy College, Nellore, Andhra Pradesh, India.
Received: February 12, 2025; Published: February 28, 2025



Cancer is the most prevalent challenging disease, among that breast cancer is the challenging malignancy with metastasis and became primary cause of mortality. Current research focus on stem cell therapy because of its ability to target and repair of damaged tissue and reverse tumorigenesis. This has emerged as a promising avenue for the treatment of breast cancer, offering potential benefits alongside significant challenges. Here we discussed the stem cell therapy leverages and its properties to intervene in cancer progression particularly in metastasis, which is resistant to conventional treatments. Stem cells can either target directly on tumor cell or by increasing the tissue repair. Here we discussed briefly the molecular mechanisms, pathways of stem cell targets in breast cancer treatment. Here we discussed the signalling pathways which were imperative in progression of breast cancer. Despite of these challenges like tumorigenicity, immune responses, and the target delivery methods remain crucial barriers to widespread clinical application. Here in this review we summarised the current progression of stem cell therapy in breast cancer.

 Keywords: Breast Cancer; Stem Cell Therapy; Tumorigenicity

  1. Haeckel E. “The evolution of ontogeny”. Journal of Developmental Biology 3 (1900): 145-159.
  2. Al-Hajj M., et al. “Prospective identification of tumorigenic breast cancer cells”. Proceedings of the National Academy of Sciences of the United States of America7 (2003): 3983-3988.
  3. Verfaillie CM. “Adult stem cells: assessing the case for pluripotency”. Trends in Cell Biology 11 (2002): 502-508.
  4. Till JE and McCulloch EA. “A direct measurement of the radiation sensitivity of normal mouse bone marrow cells”. Radiation Research 2 (1961): 213-222.
  5. Evans MJ and Kaufman MH. “Establishment in culture of pluripotential cells from mouse embryos”. Nature 5819 (1981): 154-156.
  6. Thomson JA., et al. “Embryonic stem cell lines derived from human blastocysts”. Science5391 (1998): 1145-1147.
  7. Reya T., et al. “Stem cells, cancer, and cancer stem cells”. Nature6859 (2001): 105-111.
  8. Fuchs E and Segre JA. “Stem cells: a new lease on life”. Cell 1 (2000): 143-155.
  9. Al-Hajj M., et al. “Prospective identification of tumorigenic breast cancer cells”. Proceedings of the National Academy of Sciences of the United States of America7 (2003): 3983-3988.
  10. Visvader JE and Lindeman GJ. “Cancer stem cells in solid tumours: accumulating evidence and unresolved questions”. Nature Reviews Cancer 10 (2008): 755-768.
  11. Diehn M., et al. “Association of reactive oxygen species levels and radioresistance in cancer stem cells”. Nature7239 (2009): 780-783.
  12. Li X., et al. “Intrinsic resistance of tumorigenic breast cancer cells to chemotherapy”. Journal of the National Cancer Institute 9 (2008): 672-679.
  13. Liu S., et al. “Breast cancer stem cells transition between epithelial and mesenchymal states reflective of their normal counterparts”. Stem Cell Reports 1 (2014): 78-91.
  14. Brooks MD., et al. “Therapeutic implications of cellular heterogeneity and plasticity in breast cancer”. Cell Stem Cell 3 (2015): 260-271.
  15. Hanahan D and Weinberg RA. “Hallmarks of cancer: the next generation”. Cell 5 (2011): 646-674.
  16. Nassar D and Blanpain C. “Cancer stem cells: basic concepts and therapeutic implications”. Annual Review of Pathology 11 (2016): 47-76.
  17. Zakaria N., et al. “Human non-adherent, non-sphere forming breast cancer cells exhibit stem-like cancer cell properties”. PLoS One7 (2015): e0134585.
  18. Zhan T., et al. “Wnt signaling in cancer”. Oncogene 11 (2017): 1461-1473.
  19. Andersson ER and Lendahl U. “Therapeutic modulation of Notch signalling—are we there yet?” Nature Reviews Drug Discovery5 (2014): 357-378.
  20. Briscoe J and Thérond PP. “The mechanisms of Hedgehog signalling and its roles in development and disease”. Nature Reviews Molecular Cell Biology 7 (2013): 416-429.
  21. Kasper M., et al. “GLI transcription factors: mediators of oncogenic Hedgehog signalling”. European Journal of Cancer 4 (2006): 437-445.
  22. Liu S., et al. “Hedgehog signaling and Bmi-1 regulate self-renewal of normal and malignant human mammary stem cells”. Cancer Research 12 (2006): 6063-6071.
  23. Nolan-Stevaux O., et al. “GLI1 is regulated through Smoothened-independent mechanisms in neoplastic pancreatic ducts and mediates PDAC cell survival and transformation”. Genes and Development 1 (2009): 24-36.
  24. Costa RL., et al. “Targeting the PI3K/AKT/mTOR pathway in triple-negative breast cancer: a review”. Breast Cancer Research and Treatment 3 (2018): 397-406.
  25. Mayer IA and Arteaga CL. “The PI3K/AKT pathway as a target for cancer treatment”. Annual Review of Medicine 67 (2016): 11-28.
  26. Fruman DA., et al. “The PI3K pathway in human disease”. Cell 4 (2017): 605-635.
  27. André F., et al. “Alpelisib for PIK3CA-mutated, hormone receptor-positive advanced breast cancer”. New England Journal of Medicine 20 (2019): 1929-1940.
  28. Janku F., et al. “Targeting the PI3K pathway in cancer: are we making headway?” Nature Reviews Clinical Oncology 5 (2018): 273-291.
  29. Batlle E and Clevers H. “Cancer stem cells revisited”. Nature Medicine 10 (2017): 1124-1134.
  30. Plaks V., et al. “The cancer stem cell niche: how essential is the niche in regulating stemness of tumor cells?” Cell Stem Cell3 (2015): 225-238.
  31. Flavahan WA., et al. “Epigenetic plasticity and the hallmarks of cancer”. Science6348 (2017): eaal2380.
  32. Dawson MA and Kouzarides T. “Cancer epigenetics: from mechanism to therapy”. Cell1 (2012): 12-27.
  33. Schott AF., et al. “Preclinical and clinical studies of gamma secretase inhibitors with docetaxel on human breast tumors”. Clinical Cancer Research 6 (2013): 1512-1524.
  34. Zhan T., et al. “Wnt signaling in colorectal cancer: pathogenic role and therapeutic implications”. Molecular Cancer1 (2017): 197.
  35. Reedijk M., et al. “High-level coexpression of JAG1 and NOTCH1 is observed in human breast cancer and is associated with poor overall survival”. Cancer Research 18 (2005): 8530-8537.
  36. Takebe N., et al. “Targeting cancer stem cells by inhibiting Wnt, Notch, and Hedgehog pathways”. Nature Reviews Clinical Oncology 2 (2011): 97-106.
  37. Zhang S., et al. “The role of PI3K/AKT and MAPK/ERK signaling pathways in the maintenance of stemness and tumorigenicity of glioblastoma stem-like cells”. Biochemical and Biophysical Research Communications 3 (2017): 707-713.
  38. Shipitsin M., et al. “Molecular definition of breast tumor heterogeneity”. Cancer Cell3 (2007): 259-273.
  39. Studeny M., et al. “Mesenchymal stem cells: potential precursors for tumor stroma and targeted-delivery vehicles for anticancer agents”. Journal of the National Cancer Institute 21 (2004): 1593-1603.
  40. Mader EK., et al. “Mesenchymal stem cell carriers protect oncolytic measles viruses from antibody neutralization in an orthotopic ovarian cancer therapy model”. Clinical Cancer Research 23 (2009): 7246-7255.
  41. Ning X., et al. “Therapeutic strategies targeting cancer stem cells”. Cancer Biology and Therapy 4 (2013): 295-303.
  42. Kreso A and Dick JE. “Evolution of the cancer stem cell model”. Cell Stem Cell3 (2014): 275-291.
  43. Tirino V., et al. “Cancer stem cells in solid tumors: an overview and new approaches for their isolation and characterization”. The FASEB Journal 1 (2013): 13-24.
  44. Batlle E and Clevers H. “Cancer stem cells revisited”. Nature Medicine 10 (2017): 1124-1134.
  45. Phi LTH., et al. “Cancer stem cells (CSCs) in drug resistance and their therapeutic implications in cancer treatment”. Stem Cells International (2018): 5416923.
  46. Li Y., et al. “Drug resistance and cancer stem cells”. Cell Communication and Signaling 1 (2021): 19.
  47. dos Santos SN., et al. “Molecular imaging of cancer stem cells and their role in therapy resistance”. Journal of Nuclear Medicine 1 (2025): 14-19.
  48. Li Y., et al. “Drug resistance and cancer stem cells”. Cell Communication and Signaling 1 (2021): 19.
  49. Gaggianesi M., et al. “Messing up the cancer stem cell chemoresistance mechanisms supported by tumor microenvironment”. Frontiers in Oncology 11 (2021): 702642.
  50. Turdo A., et al. “Meeting the challenge of targeting cancer stem cells”. Frontiers in Cell and Developmental Biology 7 (2019): 16.
  51. Zhou HM., et al. “Targeting cancer stem cells for reversing therapy resistance: mechanism, signalling, and prospective agents”. Signal Transduction and Targeted Therapy 6 (2021): 62.
  52. Zhang S., et al. “Cancer stem cells: a target for overcoming therapeutic resistance and relapse”. Cancer Biology and Medicine 12 (2023): 985-1020.
  53. Mengistu BA., et al. “Comprehensive review of drug resistance in mammalian cancer stem cells: implications for cancer therapy”. Cancer Cell International 1 (2024): 406.
  54. Zeng L., et al. “Breast cancer animal models and applications”. Zoological Research 5 (2020): 477-494.
  55. Atashzar MR., et al. “Cancer stem cells: A review from origin to therapeutic implications”. Journal of Cellular Physiology 2 (2020): 790-803.
  56. Landeros N., et al. “Preclinical and clinical trials of new treatment strategies targeting cancer stem cells in subtypes of breast cancer”. Cells5 (2023): 720.
  57. Boulbes DR., et al. “CD44 expression contributes to trastuzumab resistance in HER2-positive breast cancer cells”. Breast Cancer Research and Treatment 3 (2015): 501-513.
  58. Schott AF., et al. “Preclinical and clinical studies of gamma secretase inhibitors with docetaxel on human breast tumors”. Clinical Cancer Research 6 (2013): 1512-1524.
  59. Zhang X., et al. “Breast cancer stem cells: biomarkers, identification and isolation methods, regulating mechanisms, cellular origin, and beyond”. Cancers (Basel)12 (2020): 3765.
  60. Wang H., et al. “Anticancer mechanisms of salinomycin in breast cancer and its clinical applications”. Frontiers in Oncology 11 (2021): 654428.

M Suchitra., et al. “Stem Cell Therapy in Progression of Breast Cancer-An Overview” ”. EC Pharmacology and Toxicology  13.3 (2025): 01-12.