Differentiation therapy

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Medical specialty	oncology
Uses
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Differentiation therapy is an approach to treating advanced cancers in which malignant cells are encouraged to differentiate into more mature forms using pharmacological agents. The basis of the therapy stems from the tendency of malignant tumor cells to assume a less specialized, stem cell-like dedifferentiated state.<ref name=Sell2004>Sell, Stewart.,

 Stem cell origin of cancer and differentiation therapy, 
 Critical Reviews in Oncology/Hematology, 
 2004,
 Vol. 51(Issue: 1),
 pp. 1–28,
 DOI: 10.1016/j.critrevonc.2004.04.007,
 PMID: 15207251,</ref>

Leukemia

The approach was motivated by noticing that leukemia cells fail to differentiate and fully mature.<ref name=Nowak2009>,

 Differentiation therapy of leukemia: 3 decades of development, 
 Blood, 
 2009,
 Vol. 113(Issue: 16),
 pp. 3655–65,
 DOI: 10.1182/blood-2009-01-198911,
 PMID: 19221035,
 PMC: 2943835,</ref>

By 2001 encouraging clinical results were seen.<ref>,

 Differentiation therapy of human cancer: Basic science and clinical applications, 
 Pharmacology & Therapeutics, 
 2001,
 Vol. 90(Issue: 2–3),
 pp. 105–56,
 DOI: 10.1016/s0163-7258(01)00132-2,
 PMID: 11578655,</ref>

The first differentiation agent found to be successful was all-trans-retinoic acid (ATRA) in the treatment of acute promyelocytic leukemia (APL).<ref name=Sell2004/>

Other cancers

The process of cancer spreading (metastasis) involves tumour cells undergoing an epithelial-to-mesenchymal transition (EMT) to invade and spread, followed by a mesenchymal-to-epithelial transition (MET) at remote sites.

Other agents investigated (pre-clinically) to encourage MET include cholera toxin (CTx) and forskolin (Fsk).<ref name=Patt2016>,

 Activation of PKA leads to mesenchymal-to-epithelial transition and loss of tumor-initiating ability, 
 Science, 
 2016,
 Vol. 351(Issue: 6277),
 pp. aad3680,
 DOI: 10.1126/science.aad3680,
 PMID: 26941323,
 PMC: 5131720,</ref>

References

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