Differentiation therapy

Short description: Approach to treating advanced cancers

Differentiation therapy

Specialty| oncology

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Differentiation therapy is a method 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.[1]

## Leukemia

The approach was motivated by noticing that leukemia cells fail to differentiate and fully mature.[2]

By 2001 encouraging clinical results were seen.[3]

The first differentiation agent found to be successful was all-trans-retinoic acid (ATRA) in the treatment of acute promyelocytic leukemia (APL).[1]

## 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).[4]

## References

1. ↑ 1.0 1.1 Sell, Stewart. (2004). "Stem cell origin of cancer and differentiation therapy". Critical Reviews in Oncology/Hematology 51 (1): 1–28. doi:10.1016/j.critrevonc.2004.04.007. PMID 15207251.
2. ↑ Nowak, D.; Stewart, D.; Koeffler, H. P. (2009). "Differentiation therapy of leukemia: 3 decades of development". Blood 113 (16): 3655–65. doi:10.1182/blood-2009-01-198911. PMID 19221035.
3. ↑ Leszczyniecka, M; Roberts, T; Dent, P; Grant, S; Fisher, P. B. (2001). "Differentiation therapy of human cancer: Basic science and clinical applications". Pharmacology & Therapeutics 90 (2–3): 105–56. doi:10.1016/s0163-7258(01)00132-2. PMID 11578655.
4. ↑ Pattabiraman, D. R.; Bierie, B.; Kober, K. I.; Thiru, P.; Krall, J. A.; Zill, C.; Reinhardt, F.; Tam, W. L. et al. (2016). "Activation of PKA leads to mesenchymal-to-epithelial transition and loss of tumor-initiating ability". Science 351 (6277): aad3680. doi:10.1126/science.aad3680. PMID 26941323.

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