Chemotherapy Plays a Role in Relapse?
Breast cancer stem cells may be surviving therapy… because of therapy
William Aryitey |
Breast cancer that resurfaces after initial successful treatment is often metastatic (1). Major players in that recurrence are breast cancer stem cells (BCSCs) – and a study by Johns Hopkins has found that chemotherapy is actually giving BCSCs a boost (2).
BCSCs sometimes evade the barrage of cytotoxic treatment by surrounding themselves with so many cancerous cells that the therapeutics can’t reach them. Have the BCSCs simply traded in a deadly cytotoxic environment for a dangerous hypoxic one? No, because the crafty cells have another trick up their sleeve: the use of hypoxia inducible factor (HIF) proteins, which allow BCSCs to survive low-oxygen conditions.
HIF determines the gene expression of GSTO1, which in turn promotes calcium release and leads to an increase of pluripotency factors and enrichment of BCSCs. The Johns Hopkins study found that some chemotherapies, such as carboplatin, can also induce GSTO1 expression and that HIF inhibition can reduce the effects of the chemotherapy-induced BCSC enrichment.
The results shine a light on an avenue by which the cancerous cells evade treatment – and could explain why cancer often comes back more aggressively after remission. The work also adds weight to previous claims (3) that HIF inhibition alongside chemotherapy could improve clinical outcomes and hints at another potential therapeutic target: GSTO1 inhibition.
The five-year survival rate after breast cancer diagnosis is around 90 percent (4) – counteracting the negative “side effects” of chemotherapy could push the number even higher.
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- T Oskarsson et al., “Metastatic stem cells: sources, niches, and vital pathways”, Cell Stem Cell, 14, 306–321 (2014). PMID: 24607405.
- H Lu et al., “Chemotherapy-induced Ca2+ release stimulates breast cancer stem cell enrichment”, Cell rep, 18, 1946–1957 (2017). PMID: 28228260.
- D Samantha et al., “Hypoxia-inducible factors are required for chemotherapy resistance of breast cancer stem cells”, Proc Natl Acad Sci USA, 111, E5429–E5438 (2014). PMID: 25453096.
- National Cancer Institute, “Cancer stat facts: female breast cancer”, (2017). Available at: bit.ly/2iGoIHA. Accessed March 20, 2017.